Trial Outcomes & Findings for A Study of LY2189265 Compared to Sitagliptin in Participants With Type 2 Diabetes Mellitus on Metformin (NCT NCT00734474)
NCT ID: NCT00734474
Last Updated: 2015-04-20
Results Overview
Least squares (LS) means were calculated using analysis of covariance (ANCOVA) and last observation carried forward (LOCF) imputation with country and treatment as fixed effects and baseline HbA1c as a covariate.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
1202 participants
Primary outcome timeframe
Baseline, 52 weeks
Results posted on
2015-04-20
Participant Flow
Participant milestones
| Measure |
3.0 mg LY2189265
LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)
|
2.0 mg LY2189265
LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)
|
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
15
|
30
|
304
|
10
|
302
|
25
|
24
|
315
|
177
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
15
|
30
|
304
|
10
|
302
|
25
|
24
|
315
|
177
|
|
Overall Study
Entered Study Before Dose Decision Point
|
15
|
30
|
25
|
10
|
21
|
25
|
24
|
42
|
38
|
|
Overall Study
Completed Up to Dose Decision Point
|
8
|
25
|
24
|
8
|
21
|
21
|
23
|
42
|
34
|
|
Overall Study
Entered Study After Dose Decision Point
|
0
|
0
|
279
|
0
|
281
|
0
|
0
|
273
|
139
|
|
Overall Study
Completed 26-Week Visit
|
0
|
0
|
258
|
2
|
268
|
2
|
2
|
270
|
124
|
|
Overall Study
Completed 52-Week Visit
|
0
|
0
|
238
|
0
|
243
|
0
|
0
|
238
|
112
|
|
Overall Study
COMPLETED
|
0
|
0
|
192
|
0
|
184
|
0
|
0
|
186
|
95
|
|
Overall Study
NOT COMPLETED
|
15
|
30
|
112
|
10
|
118
|
25
|
24
|
129
|
82
|
Reasons for withdrawal
| Measure |
3.0 mg LY2189265
LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)
|
2.0 mg LY2189265
LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)
|
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|
|
Overall Study
Entry Criteria Not Met
|
0
|
0
|
5
|
0
|
3
|
1
|
0
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
13
|
0
|
11
|
1
|
0
|
9
|
4
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
18
|
0
|
24
|
2
|
0
|
36
|
21
|
|
Overall Study
Physician Decision
|
0
|
0
|
4
|
1
|
11
|
0
|
0
|
9
|
9
|
|
Overall Study
Adverse Event
|
4
|
4
|
63
|
1
|
64
|
0
|
1
|
65
|
39
|
|
Overall Study
Protocol Violation
|
0
|
0
|
4
|
0
|
3
|
0
|
0
|
3
|
1
|
|
Overall Study
Sponsor Decision, Arm Discontinued
|
8
|
25
|
0
|
8
|
0
|
21
|
23
|
0
|
0
|
|
Overall Study
Sponsor Decision
|
0
|
0
|
0
|
0
|
2
|
0
|
0
|
0
|
0
|
|
Overall Study
Death
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
2
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
4
|
0
|
0
|
0
|
0
|
4
|
6
|
Baseline Characteristics
A Study of LY2189265 Compared to Sitagliptin in Participants With Type 2 Diabetes Mellitus on Metformin
Baseline characteristics by cohort
| Measure |
3.0 mg LY2189265
n=15 Participants
LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)
|
2.0 mg LY2189265
n=30 Participants
LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)
|
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=10 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
n=25 Participants
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
n=24 Participants
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin
n=177 Participants
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Total
n=1202 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
52.81 years
STANDARD_DEVIATION 10.66 • n=99 Participants
|
52.56 years
STANDARD_DEVIATION 10.95 • n=107 Participants
|
53.66 years
STANDARD_DEVIATION 10.02 • n=206 Participants
|
55.38 years
STANDARD_DEVIATION 8.71 • n=7 Participants
|
54.35 years
STANDARD_DEVIATION 9.81 • n=31 Participants
|
54.70 years
STANDARD_DEVIATION 9.72 • n=30 Participants
|
56.51 years
STANDARD_DEVIATION 6.56 • n=3 Participants
|
53.75 years
STANDARD_DEVIATION 10.27 • n=6 Participants
|
54.91 years
STANDARD_DEVIATION 9.05 • n=114 Participants
|
54.09 years
STANDARD_DEVIATION 9.85
|
|
Sex: Female, Male
Female
|
10 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
158 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
168 Participants
n=31 Participants
|
12 Participants
n=30 Participants
|
15 Participants
n=3 Participants
|
164 Participants
n=6 Participants
|
87 Participants
n=114 Participants
|
643 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
146 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
134 Participants
n=31 Participants
|
13 Participants
n=30 Participants
|
9 Participants
n=3 Participants
|
151 Participants
n=6 Participants
|
90 Participants
n=114 Participants
|
559 Participants
|
|
Race/Ethnicity, Customized
Aboriginal and/or Torres Strait Islander
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
0 participants
n=31 Participants
|
0 participants
n=30 Participants
|
0 participants
n=3 Participants
|
1 participants
n=6 Participants
|
0 participants
n=114 Participants
|
1 participants
|
|
Race/Ethnicity, Customized
African
|
1 participants
n=99 Participants
|
3 participants
n=107 Participants
|
16 participants
n=206 Participants
|
0 participants
n=7 Participants
|
12 participants
n=31 Participants
|
2 participants
n=30 Participants
|
0 participants
n=3 Participants
|
7 participants
n=6 Participants
|
9 participants
n=114 Participants
|
50 participants
|
|
Race/Ethnicity, Customized
Caucasian
|
7 participants
n=99 Participants
|
13 participants
n=107 Participants
|
157 participants
n=206 Participants
|
4 participants
n=7 Participants
|
162 participants
n=31 Participants
|
9 participants
n=30 Participants
|
12 participants
n=3 Participants
|
158 participants
n=6 Participants
|
91 participants
n=114 Participants
|
613 participants
|
|
Race/Ethnicity, Customized
East Asian
|
0 participants
n=99 Participants
|
6 participants
n=107 Participants
|
50 participants
n=206 Participants
|
0 participants
n=7 Participants
|
47 participants
n=31 Participants
|
0 participants
n=30 Participants
|
5 participants
n=3 Participants
|
52 participants
n=6 Participants
|
28 participants
n=114 Participants
|
188 participants
|
|
Race/Ethnicity, Customized
Hispanic
|
7 participants
n=99 Participants
|
8 participants
n=107 Participants
|
54 participants
n=206 Participants
|
6 participants
n=7 Participants
|
51 participants
n=31 Participants
|
14 participants
n=30 Participants
|
6 participants
n=3 Participants
|
67 participants
n=6 Participants
|
38 participants
n=114 Participants
|
251 participants
|
|
Race/Ethnicity, Customized
Native American
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
0 participants
n=31 Participants
|
0 participants
n=30 Participants
|
0 participants
n=3 Participants
|
1 participants
n=6 Participants
|
0 participants
n=114 Participants
|
1 participants
|
|
Race/Ethnicity, Customized
West Asian (Indian sub-continent)
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
27 participants
n=206 Participants
|
0 participants
n=7 Participants
|
30 participants
n=31 Participants
|
0 participants
n=30 Participants
|
1 participants
n=3 Participants
|
28 participants
n=6 Participants
|
11 participants
n=114 Participants
|
97 participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
0 participants
n=31 Participants
|
0 participants
n=30 Participants
|
0 participants
n=3 Participants
|
1 participants
n=6 Participants
|
0 participants
n=114 Participants
|
1 participants
|
|
Region of Enrollment
United States
|
9 participants
n=99 Participants
|
17 participants
n=107 Participants
|
73 participants
n=206 Participants
|
4 participants
n=7 Participants
|
83 participants
n=31 Participants
|
10 participants
n=30 Participants
|
7 participants
n=3 Participants
|
80 participants
n=6 Participants
|
46 participants
n=114 Participants
|
329 participants
|
|
Region of Enrollment
Taiwan
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
19 participants
n=206 Participants
|
0 participants
n=7 Participants
|
18 participants
n=31 Participants
|
0 participants
n=30 Participants
|
3 participants
n=3 Participants
|
20 participants
n=6 Participants
|
12 participants
n=114 Participants
|
73 participants
|
|
Region of Enrollment
Spain
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
10 participants
n=206 Participants
|
0 participants
n=7 Participants
|
11 participants
n=31 Participants
|
0 participants
n=30 Participants
|
0 participants
n=3 Participants
|
11 participants
n=6 Participants
|
4 participants
n=114 Participants
|
36 participants
|
|
Region of Enrollment
Russian Federation
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
21 participants
n=206 Participants
|
0 participants
n=7 Participants
|
18 participants
n=31 Participants
|
0 participants
n=30 Participants
|
0 participants
n=3 Participants
|
17 participants
n=6 Participants
|
8 participants
n=114 Participants
|
64 participants
|
|
Region of Enrollment
India
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
27 participants
n=206 Participants
|
0 participants
n=7 Participants
|
29 participants
n=31 Participants
|
0 participants
n=30 Participants
|
0 participants
n=3 Participants
|
28 participants
n=6 Participants
|
12 participants
n=114 Participants
|
96 participants
|
|
Region of Enrollment
France
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
12 participants
n=206 Participants
|
0 participants
n=7 Participants
|
14 participants
n=31 Participants
|
0 participants
n=30 Participants
|
0 participants
n=3 Participants
|
12 participants
n=6 Participants
|
8 participants
n=114 Participants
|
46 participants
|
|
Region of Enrollment
Mexico
|
3 participants
n=99 Participants
|
3 participants
n=107 Participants
|
32 participants
n=206 Participants
|
5 participants
n=7 Participants
|
30 participants
n=31 Participants
|
10 participants
n=30 Participants
|
6 participants
n=3 Participants
|
35 participants
n=6 Participants
|
27 participants
n=114 Participants
|
151 participants
|
|
Region of Enrollment
Puerto Rico
|
1 participants
n=99 Participants
|
2 participants
n=107 Participants
|
12 participants
n=206 Participants
|
0 participants
n=7 Participants
|
5 participants
n=31 Participants
|
3 participants
n=30 Participants
|
0 participants
n=3 Participants
|
10 participants
n=6 Participants
|
7 participants
n=114 Participants
|
40 participants
|
|
Region of Enrollment
Canada
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
13 participants
n=206 Participants
|
0 participants
n=7 Participants
|
11 participants
n=31 Participants
|
0 participants
n=30 Participants
|
0 participants
n=3 Participants
|
12 participants
n=6 Participants
|
6 participants
n=114 Participants
|
42 participants
|
|
Region of Enrollment
Poland
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
20 participants
n=206 Participants
|
0 participants
n=7 Participants
|
23 participants
n=31 Participants
|
2 participants
n=30 Participants
|
2 participants
n=3 Participants
|
23 participants
n=6 Participants
|
12 participants
n=114 Participants
|
83 participants
|
|
Region of Enrollment
Romania
|
1 participants
n=99 Participants
|
2 participants
n=107 Participants
|
7 participants
n=206 Participants
|
1 participants
n=7 Participants
|
4 participants
n=31 Participants
|
0 participants
n=30 Participants
|
4 participants
n=3 Participants
|
8 participants
n=6 Participants
|
5 participants
n=114 Participants
|
32 participants
|
|
Region of Enrollment
Germany
|
0 participants
n=99 Participants
|
0 participants
n=107 Participants
|
31 participants
n=206 Participants
|
0 participants
n=7 Participants
|
31 participants
n=31 Participants
|
0 participants
n=30 Participants
|
0 participants
n=3 Participants
|
28 participants
n=6 Participants
|
15 participants
n=114 Participants
|
105 participants
|
|
Region of Enrollment
Korea, Republic of
|
0 participants
n=99 Participants
|
5 participants
n=107 Participants
|
27 participants
n=206 Participants
|
0 participants
n=7 Participants
|
25 participants
n=31 Participants
|
0 participants
n=30 Participants
|
2 participants
n=3 Participants
|
31 participants
n=6 Participants
|
15 participants
n=114 Participants
|
105 participants
|
|
Body Weight
|
85.09 kilograms
STANDARD_DEVIATION 14.25 • n=99 Participants
|
86.56 kilograms
STANDARD_DEVIATION 18.33 • n=107 Participants
|
86.67 kilograms
STANDARD_DEVIATION 17.45 • n=206 Participants
|
89.48 kilograms
STANDARD_DEVIATION 18.06 • n=7 Participants
|
86.22 kilograms
STANDARD_DEVIATION 17.99 • n=31 Participants
|
88.84 kilograms
STANDARD_DEVIATION 14.98 • n=30 Participants
|
81.94 kilograms
STANDARD_DEVIATION 17.67 • n=3 Participants
|
85.97 kilograms
STANDARD_DEVIATION 16.91 • n=6 Participants
|
87.07 kilograms
STANDARD_DEVIATION 16.86 • n=114 Participants
|
86.38 kilograms
STANDARD_DEVIATION 17.28
|
|
Body Mass Index (BMI)
|
31.02 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.69 • n=99 Participants
|
31.45 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.88 • n=107 Participants
|
31.40 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.57 • n=206 Participants
|
33.89 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.44 • n=7 Participants
|
31.15 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.44 • n=31 Participants
|
32.53 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.61 • n=30 Participants
|
31.06 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 3.94 • n=3 Participants
|
31.02 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.20 • n=6 Participants
|
31.37 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.25 • n=114 Participants
|
31.27 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.39
|
|
Glycosylated Hemoglobin (HbA1c)
|
7.95 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.11 • n=99 Participants
|
8.36 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.04 • n=107 Participants
|
8.12 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.05 • n=206 Participants
|
7.87 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.62 • n=7 Participants
|
8.19 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.11 • n=31 Participants
|
8.30 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.34 • n=30 Participants
|
7.82 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.80 • n=3 Participants
|
8.09 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.09 • n=6 Participants
|
8.10 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.14 • n=114 Participants
|
8.13 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.09
|
|
Duration of Diabetes
|
6.79 years
STANDARD_DEVIATION 6.34 • n=99 Participants
|
6.92 years
STANDARD_DEVIATION 5.12 • n=107 Participants
|
6.95 years
STANDARD_DEVIATION 5.50 • n=206 Participants
|
7.04 years
STANDARD_DEVIATION 4.57 • n=7 Participants
|
7.34 years
STANDARD_DEVIATION 4.92 • n=31 Participants
|
6.75 years
STANDARD_DEVIATION 3.99 • n=30 Participants
|
6.74 years
STANDARD_DEVIATION 4.20 • n=3 Participants
|
7.16 years
STANDARD_DEVIATION 4.89 • n=6 Participants
|
6.96 years
STANDARD_DEVIATION 5.43 • n=114 Participants
|
7.09 years
STANDARD_DEVIATION 5.12
|
|
Fasting Plasma Glucose
|
NA millimoles per liter (mmol/L)
STANDARD_DEVIATION NA • n=99 Participants
|
NA millimoles per liter (mmol/L)
STANDARD_DEVIATION NA • n=107 Participants
|
9.75 millimoles per liter (mmol/L)
STANDARD_DEVIATION 3.27 • n=206 Participants
|
NA millimoles per liter (mmol/L)
STANDARD_DEVIATION NA • n=7 Participants
|
9.68 millimoles per liter (mmol/L)
STANDARD_DEVIATION 2.94 • n=31 Participants
|
NA millimoles per liter (mmol/L)
STANDARD_DEVIATION NA • n=30 Participants
|
NA millimoles per liter (mmol/L)
STANDARD_DEVIATION NA • n=3 Participants
|
9.56 millimoles per liter (mmol/L)
STANDARD_DEVIATION 2.80 • n=6 Participants
|
9.86 millimoles per liter (mmol/L)
STANDARD_DEVIATION 3.15 • n=114 Participants
|
NA millimoles per liter (mmol/L)
STANDARD_DEVIATION NA
|
PRIMARY outcome
Timeframe: Baseline, 52 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms who had evaluable HbA1c data. Last observation carried forward was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Least squares (LS) means were calculated using analysis of covariance (ANCOVA) and last observation carried forward (LOCF) imputation with country and treatment as fixed effects and baseline HbA1c as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=301 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=297 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=311 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Glycosylated Hemoglobin (HbA1c) Change From Baseline
|
-1.10 percentage of HbA1c
Standard Error 0.06
|
-0.87 percentage of HbA1c
Standard Error 0.06
|
-0.39 percentage of HbA1c
Standard Error 0.06
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 27.4 weeksPopulation: All participants randomized before the dose decision point who had evaluable HbA1c data.
Change from baseline in HbA1c was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the decision point was 27.4 weeks.
Outcome measures
| Measure |
1.5 mg LY2189265
n=10 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=26 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=20 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=8 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
n=20 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
n=21 Participants
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
n=14 Participants
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
n=30 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
n=28 Participants
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at the Dose Decision Point
|
-1.09 percentage of HbA1c
Standard Deviation 0.77
|
-1.25 percentage of HbA1c
Standard Deviation 0.68
|
-1.49 percentage of HbA1c
Standard Deviation 1.12
|
-0.98 percentage of HbA1c
Standard Deviation 0.47
|
-1.02 percentage of HbA1c
Standard Deviation 0.99
|
-0.94 percentage of HbA1c
Standard Deviation 0.65
|
-0.70 percentage of HbA1c
Standard Deviation 0.49
|
-0.76 percentage of HbA1c
Standard Deviation 0.86
|
-0.06 percentage of HbA1c
Standard Deviation 0.64
|
—
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable HbA1c data. Last observation carried forward was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Least squares (LS) means were calculated using analysis of covariance (ANCOVA) and last observation carried forward (LOCF) imputation with country and treatment as fixed effects and baseline HbA1c as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=301 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=297 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=311 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=176 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Glycosylated Hemoglobin (HbA1c) Change From Baseline
26 Weeks
|
-1.22 percentage of HbA1c
Standard Error 0.05
|
-1.01 percentage of HbA1c
Standard Error 0.06
|
-0.61 percentage of HbA1c
Standard Error 0.05
|
0.03 percentage of HbA1c
Standard Error 0.07
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Glycosylated Hemoglobin (HbA1c) Change From Baseline
104 Weeks
|
-0.99 percentage of HbA1c
Standard Error 0.06
|
-0.71 percentage of HbA1c
Standard Error 0.07
|
-0.32 percentage of HbA1c
Standard Error 0.06
|
NA percentage of HbA1c
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 13, 26, 52, and 104 weeksPopulation: All participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms randomized after the dose decision point who had evaluable HbA1c data. If there were no data after the date of randomization, the endpoint was considered missing.
Durability of effect on HbA1c was assessed by comparing the differences in mean change from baseline in HbA1c at 1 time point versus an earlier time point. Least squares (LS) means of change from baseline HbA1c data were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=303 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=314 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Durability of Change From Baseline in Glycosylated Hemoglobin (HbA1c)
26 Weeks Versus 13 Weeks (n=269, 269, 276, 136)
|
-0.03 percentage of HbA1c
Standard Error 0.04
|
0.02 percentage of HbA1c
Standard Error 0.04
|
0.00 percentage of HbA1c
Standard Error 0.04
|
-0.14 percentage of HbA1c
Standard Error 0.05
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Durability of Change From Baseline in Glycosylated Hemoglobin (HbA1c)
52 Weeks Versus 26 Weeks (n=245, 254, 250)
|
0.14 percentage of HbA1c
Standard Error 0.05
|
0.16 percentage of HbA1c
Standard Error 0.05
|
0.24 percentage of HbA1c
Standard Error 0.05
|
NA percentage of HbA1c
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Durability of Change From Baseline in Glycosylated Hemoglobin (HbA1c)
104 Weeks Versus 52 Weeks (n=194, 191, 190)
|
0.13 percentage of HbA1c
Standard Error 0.06
|
0.16 percentage of HbA1c
Standard Error 0.06
|
0.09 percentage of HbA1c
Standard Error 0.06
|
NA percentage of HbA1c
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 26, 52, and 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable fasting plasma glucose data. If there were no data after the date of randomization, the endpoint was considered missing.
Least squares (LS) means of change from baseline were calculated using mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=297 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=296 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=308 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=176 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Fasting Blood Glucose Change From Baseline
26 Weeks (n=265, 271, 276, 135)
|
-2.38 millimoles per liter (mmol/L)
Standard Error 0.12
|
-1.97 millimoles per liter (mmol/L)
Standard Error 0.12
|
-0.97 millimoles per liter (mmol/L)
Standard Error 0.11
|
-0.49 millimoles per liter (mmol/L)
Standard Error 0.16
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Fasting Blood Glucose Change From Baseline
52 Weeks (n=239, 247, 244)
|
-2.38 millimoles per liter (mmol/L)
Standard Error 0.13
|
-1.63 millimoles per liter (mmol/L)
Standard Error 0.13
|
-0.90 millimoles per liter (mmol/L)
Standard Error 0.13
|
NA millimoles per liter (mmol/L)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Fasting Blood Glucose Change From Baseline
104 Weeks (n=190, 187, 181)
|
-1.99 millimoles per liter (mmol/L)
Standard Error 0.15
|
-1.39 millimoles per liter (mmol/L)
Standard Error 0.15
|
-0.47 millimoles per liter (mmol/L)
Standard Error 0.15
|
NA millimoles per liter (mmol/L)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 26, 52, and 104 weeksPopulation: All participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms randomized after the dose decision point who had evaluable fasting insulin data. If there were no data after the date of randomization, the endpoint was considered missing.
Least squares (LS) means of change from baseline fasting insulin data were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=254 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=261 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=247 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=122 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Fasting Insulin Change From Baseline
26 Weeks (n=238, 249, 230, 115)
|
11.59 picomoles per liter (pmol/L)
Standard Error 6.57
|
10.15 picomoles per liter (pmol/L)
Standard Error 6.51
|
8.48 picomoles per liter (pmol/L)
Standard Error 6.68
|
-6.92 picomoles per liter (pmol/L)
Standard Error 9.24
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Fasting Insulin Change From Baseline
52 Weeks (n=207, 218, 200)
|
10.57 picomoles per liter (pmol/L)
Standard Error 5.95
|
12.95 picomoles per liter (pmol/L)
Standard Error 5.88
|
4.18 picomoles per liter (pmol/L)
Standard Error 6.01
|
NA picomoles per liter (pmol/L)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Fasting Insulin Change From Baseline
104 Weeks (n=187, 200, 183)
|
11.36 picomoles per liter (pmol/L)
Standard Error 7.58
|
21.56 picomoles per liter (pmol/L)
Standard Error 7.40
|
0.29 picomoles per liter (pmol/L)
Standard Error 7.64
|
NA picomoles per liter (pmol/L)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 27.4 weeksPopulation: All participants randomized before the dose decision point who had evaluable body weight data.
Change from baseline in body weight was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the decision point was 27.4 weeks.
Outcome measures
| Measure |
1.5 mg LY2189265
n=14 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=30 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=23 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=9 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
n=20 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
n=22 Participants
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
n=17 Participants
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
n=35 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
n=33 Participants
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Body Weight at Dose Decision Point
|
-3.32 kilograms (kg)
Standard Deviation 3.37
|
-2.15 kilograms (kg)
Standard Deviation 1.97
|
-2.12 kilograms (kg)
Standard Deviation 1.93
|
-2.23 kilograms (kg)
Standard Deviation 1.63
|
-1.17 kilograms (kg)
Standard Deviation 2.30
|
-1.53 kilograms (kg)
Standard Deviation 1.88
|
-0.85 kilograms (kg)
Standard Deviation 1.47
|
-0.43 kilograms (kg)
Standard Deviation 1.78
|
-0.56 kilograms (kg)
Standard Deviation 1.69
|
—
|
SECONDARY outcome
Timeframe: Baseline, 26, 52, and 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable body weight data. Last observation carried forward was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Least squares (LS) means of change from baseline body weight were calculated using analysis of covariance (ANCOVA) and last observation carried forward (LOCF) imputation with country and treatment as fixed effects and baseline as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=303 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=299 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=314 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Body Weight Change From Baseline
104 Weeks
|
-2.88 kilograms (kg)
Standard Error 0.25
|
-2.39 kilograms (kg)
Standard Error 0.26
|
-1.75 kilograms (kg)
Standard Error 0.25
|
NA kilograms (kg)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Body Weight Change From Baseline
26 Weeks
|
-3.18 kilograms (kg)
Standard Error 0.18
|
-2.63 kilograms (kg)
Standard Error 0.19
|
-1.46 kilograms (kg)
Standard Error 0.18
|
-1.47 kilograms (kg)
Standard Error 0.24
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Body Weight Change From Baseline
52 Weeks
|
-3.03 kilograms (kg)
Standard Error 0.22
|
-2.60 kilograms (kg)
Standard Error 0.23
|
-1.53 kilograms (kg)
Standard Error 0.22
|
NA kilograms (kg)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 13, 26, 52, and 104 weeksPopulation: All participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms randomized after the dose decision point who had evaluable body weight data. If there were no data after the date of randomization, the endpoint was considered missing.
Durability of effect on body weight was assessed by comparing the differences in mean change from baseline in body weight at 1 time point versus an earlier time point. Least squares (LS) means of change from baseline body weight data were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Durability of Change From Baseline Body Weight
26 Weeks Versus 13 Weeks (n=271, 278, 282, 138)
|
-0.53 kilograms (kg)
Standard Error 0.14
|
-0.57 kilograms (kg)
Standard Error 0.14
|
-0.42 kilograms (kg)
Standard Error 0.13
|
-0.37 kilograms (kg)
Standard Error 0.18
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Durability of Change From Baseline Body Weight
52 Weeks Versus 26 Weeks (n=246, 255, 253)
|
0.17 kilograms (kg)
Standard Error 0.18
|
0.06 kilograms (kg)
Standard Error 0.18
|
-0.04 kilograms (kg)
Standard Error 0.18
|
NA kilograms (kg)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Durability of Change From Baseline Body Weight
104 Weeks Versus 26 Weeks (n=197, 192, 191)
|
0.42 kilograms (kg)
Standard Error 0.23
|
0.32 kilograms (kg)
Standard Error 0.24
|
-0.39 kilograms (kg)
Standard Error 0.23
|
NA kilograms (kg)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 26, 52, and 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable waist circumference data. If there were no data after the date of randomization, the endpoint was considered missing.
Least squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=299 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=301 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=312 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=175 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Waist Circumference Change From Baseline
26 Weeks (n=266, 273, 277, 138)
|
-2.89 centimeters (cm)
Standard Error 0.24
|
-1.78 centimeters (cm)
Standard Error 0.24
|
-1.45 centimeters (cm)
Standard Error 0.24
|
-1.20 centimeters (cm)
Standard Error 0.32
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Waist Circumference Change From Baseline
52 Weeks (n=238, 250, 247)
|
-2.91 centimeters (cm)
Standard Error 0.29
|
-2.05 centimeters (cm)
Standard Error 0.29
|
-1.45 centimeters (cm)
Standard Error 0.29
|
NA centimeters (cm)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Waist Circumference Change From Baseline
104 Weeks (n=192, 189, 188)
|
-2.57 centimeters (cm)
Standard Error 0.35
|
-1.75 centimeters (cm)
Standard Error 0.35
|
-1.20 centimeters (cm)
Standard Error 0.35
|
NA centimeters (cm)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 26, 52, and 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable HbA1c data. Last observation carried forward was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
The percentage of participants achieving HbA1c levels \<7.0% and ≤6.5% was analyzed using a logistic regression model and last observation carried forward (LOCF) imputation with baseline, country, and treatment as factors included in the model.
Outcome measures
| Measure |
1.5 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=297 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=312 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=176 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5%
<7.0% at 52 Weeks
|
57.6 percentage of participants
|
48.8 percentage of participants
|
33.0 percentage of participants
|
NA percentage of participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5%
<7.0% at 26 Weeks
|
60.9 percentage of participants
|
55.2 percentage of participants
|
37.8 percentage of participants
|
21.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5%
<7.0% at 104 Weeks
|
54.3 percentage of participants
|
44.8 percentage of participants
|
31.1 percentage of participants
|
NA percentage of participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5%
≤6.5% at 26 Weeks
|
46.7 percentage of participants
|
31.0 percentage of participants
|
21.8 percentage of participants
|
12.5 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5%
≤6.5% at 52 Weeks
|
41.7 percentage of participants
|
29.0 percentage of participants
|
19.2 percentage of participants
|
NA percentage of participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5%
≤6.5% at 104 Weeks
|
39.1 percentage of participants
|
24.2 percentage of participants
|
14.1 percentage of participants
|
NA percentage of participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 26 and 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms.
Hypoglycemic episodes (HE) were classified as severe (defined as episodes requiring assistance from another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia and has a plasma glucose level of ≤3.9 millimoles per liter \[mmol/L\]), asymptomatic (defined as episodes not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of ≤3.9 mmol/L), nocturnal (defined as any episode that occurred between bedtime and waking), or probable symptomatic (defined as episodes during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of participants with self-reported hypoglycemic events is summarized cumulatively.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Incidence of Hypoglycemic Episodes
Severe HE, 26 Weeks
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Incidence of Hypoglycemic Episodes
Severe HE, 104 Weeks
|
0 participants
|
0 participants
|
0 participants
|
NA participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Incidence of Hypoglycemic Episodes
Documented Symptomatic HE, 26 Weeks
|
17 participants
|
8 participants
|
10 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Incidence of Hypoglycemic Episodes
Documented Symptomatic HE, 104 Weeks
|
33 participants
|
19 participants
|
18 participants
|
NA participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Incidence of Hypoglycemic Episodes
Asymptomatic HE, 26 Weeks
|
5 participants
|
5 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Incidence of Hypoglycemic Episodes
Asymptomatic HE, 104 Weeks
|
9 participants
|
9 participants
|
3 participants
|
NA participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Incidence of Hypoglycemic Episodes
Nocturnal HE, 26 Weeks
|
7 participants
|
5 participants
|
2 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Incidence of Hypoglycemic Episodes
Nocturnal HE, 104 Weeks
|
14 participants
|
13 participants
|
10 participants
|
NA participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Incidence of Hypoglycemic Episodes
Probable HE, 26 Weeks
|
5 participants
|
0 participants
|
2 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Incidence of Hypoglycemic Episodes
Probable HE, 104 Weeks
|
6 participants
|
2 participants
|
6 participants
|
NA participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 26 and 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms.
Hypoglycemic episodes (HE) were classified as severe (defined as episodes requiring assistance from another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia and has a plasma glucose level of ≤3.9 millimoles per liter \[mmol/L\]), asymptomatic (defined as episodes not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of ≤3.9 mmol/L), nocturnal (defined as any episode that occurred between bedtime and waking), or probable symptomatic (defined as episodes during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of HE is summarized cumulatively.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Rate of Hypoglycemic Episodes
Probable Symptomatic HE, 26 Weeks
|
0.0 episodes per participant per year
Standard Deviation 0.4
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
0.0 episodes per participant per year
Standard Deviation 0.2
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Rate of Hypoglycemic Episodes
Probable Symptomatic HE, 104 Weeks
|
0.0 episodes per participant per year
Standard Deviation 0.1
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
0.0 episodes per participant per year
Standard Deviation 0.1
|
NA episodes per participant per year
Standard Deviation NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Rate of Hypoglycemic Episodes
Severe HE, 26 Weeks
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Rate of Hypoglycemic Episodes
Severe HE, 104 Weeks
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
NA episodes per participant per year
Standard Deviation NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Rate of Hypoglycemic Episodes
Documented Symptomatic HE, 26 Weeks
|
0.3 episodes per participant per year
Standard Deviation 1.5
|
0.1 episodes per participant per year
Standard Deviation 0.9
|
0.1 episodes per participant per year
Standard Deviation 0.7
|
0.1 episodes per participant per year
Standard Deviation 0.9
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Rate of Hypoglycemic Episodes
Documented Symptomatic HE, 104 Weeks
|
0.2 episodes per participant per year
Standard Deviation 0.9
|
0.2 episodes per participant per year
Standard Deviation 1.9
|
0.2 episodes per participant per year
Standard Deviation 1.4
|
NA episodes per participant per year
Standard Deviation NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Rate of Hypoglycemic Episodes
Asymptomatic HE, 26 Weeks
|
0.1 episodes per participant per year
Standard Deviation 0.8
|
0.1 episodes per participant per year
Standard Deviation 0.5
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Rate of Hypoglycemic Episodes
Asymptomatic HE, 104 Weeks
|
0.1 episodes per participant per year
Standard Deviation 0.4
|
0.0 episodes per participant per year
Standard Deviation 0.2
|
0.0 episodes per participant per year
Standard Deviation 0.1
|
NA episodes per participant per year
Standard Deviation NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Rate of Hypoglycemic Episodes
Nocturnal HE, 26 Weeks
|
0.1 episodes per participant per year
Standard Deviation 0.9
|
0.1 episodes per participant per year
Standard Deviation 0.6
|
0.0 episodes per participant per year
Standard Deviation 0.4
|
0.0 episodes per participant per year
Standard Deviation 0.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Rate of Hypoglycemic Episodes
Nocturnal HE, 104 Weeks
|
0.1 episodes per participant per year
Standard Deviation 0.5
|
0.0 episodes per participant per year
Standard Deviation 0.2
|
0.1 episodes per participant per year
Standard Deviation 0.5
|
NA episodes per participant per year
Standard Deviation NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 26, 52, and 104 weeksPopulation: All participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms randomized after the dose decision point and who had evaluable HOMA2 data. If there were no data after the date of randomization, the endpoint was considered missing.
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-%B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-%S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S), as percentages of a normal reference population (normal young adults). The normal reference population for both HOMA2-%B and HOMA2-%S were set at 100%. Least squares (LS) means of change from baseline of C-peptide based HOMA2-%B and HOMA2-%S were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=242 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=251 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=238 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=115 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Beta Cell Function and Insulin Sensitivity (HOMA2)
HOMA2-%B, 26 Weeks (n=206, 226, 206, 84)
|
32.28 HOMA2-%
Standard Error 2.67
|
26.98 HOMA2-%
Standard Error 2.60
|
10.81 HOMA2-%
Standard Error 2.66
|
1.60 HOMA2-%
Standard Error 4.02
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Beta Cell Function and Insulin Sensitivity (HOMA2)
HOMA2-%B, 52 Weeks (n=188, 198, 180)
|
33.57 HOMA2-%
Standard Error 2.51
|
22.30 HOMA2-%
Standard Error 2.47
|
6.66 HOMA2-%
Standard Error 2.53
|
NA HOMA2-%
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Beta Cell Function and Insulin Sensitivity (HOMA2)
HOMA2-%B, 104 Weeks (n=148, 154, 134)
|
30.89 HOMA2-%
Standard Error 3.05
|
19.11 HOMA2-%
Standard Error 3.00
|
1.47 HOMA2-%
Standard Error 3.15
|
NA HOMA2-%
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Beta Cell Function and Insulin Sensitivity (HOMA2)
HOMA2-%S, 26 Weeks (n=206, 226, 206, 84)
|
5.75 HOMA2-%
Standard Error 2.34
|
0.78 HOMA2-%
Standard Error 2.28
|
2.29 HOMA2-%
Standard Error 2.33
|
9.82 HOMA2-%
Standard Error 3.50
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Beta Cell Function and Insulin Sensitivity (HOMA2)
HOMA2-%S, 52 Weeks (n=188, 198, 180)
|
4.69 HOMA2-%
Standard Error 2.35
|
2.28 HOMA2-%
Standard Error 2.32
|
4.25 HOMA2-%
Standard Error 2.37
|
NA HOMA2-%
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Beta Cell Function and Insulin Sensitivity (HOMA2)
HOMA2-%S, 104 Weeks (n=148, 154, 134)
|
3.82 HOMA2-%
Standard Error 3.00
|
-0.12 HOMA2-%
Standard Error 2.95
|
5.61 HOMA2-%
Standard Error 3.11
|
NA HOMA2-%
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 26 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms.
A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with 1 or more TEAEs is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events at 26 Weeks
|
208 participants
|
204 participants
|
185 participants
|
111 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 52 weeksPopulation: All randomized participants in the LY2189265 and active comparator (Sitagliptin) arms.
A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with 1 or more TEAEs is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
1.5 mg LY2189265
n=15 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=30 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=304 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=10 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
n=25 Participants
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
n=24 Participants
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events at 52 Weeks
|
9 participants
|
20 participants
|
233 participants
|
8 participants
|
231 participants
|
15 participants
|
10 participants
|
219 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms.
A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with 1 or more TEAEs is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events at 104 Weeks
|
259 participants
|
255 participants
|
242 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 26 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms with baseline value not in the specified direction of treatment-emergent abnormality and at least 1 postbaseline result.
The number of participants with treatment-emergent abnormal laboratory results (defined as abnormalities that first occur after baseline) was summarized cumulatively for alkaline phosphatase, alanine aminotransferase or serum glutamic pyruvic transaminase (ALT/SGPT), amylase (pancreatic and total), aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT), basophils, bilirubin (direct and total), calcitonin, chloride, creatine phosphokinase (CPK), creatinine, creatinine clearance, eosinophils, erythrocytes, gamma glutamyltransferase (GGT), hematocrit, hemoglobin, leukocytes, lipase, lymphocytes, mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), monocytes, neutrophils, platelets, potassium, sodium, urea nitrogen, and urine microalbumin-to-creatinine ratio (UMCR).
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Bilirubin Direct, High (n=295, 291, 307, 171)
|
1 participants
|
1 participants
|
1 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Alkaline Phosphatase (n=276, 258, 281, 162)
|
9 participants
|
3 participants
|
12 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
ALT/SGPT (n=232, 237, 244, 128)
|
18 participants
|
24 participants
|
25 participants
|
8 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Amylase Pancreatic, High (n=283, 277, 295, 160)
|
54 participants
|
55 participants
|
42 participants
|
18 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Amylase Total (n=266, 265, 277, 143)
|
33 participants
|
33 participants
|
27 participants
|
13 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
AST/SGOT (n=273, 269, 284, 148)
|
14 participants
|
12 participants
|
18 participants
|
7 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Basophils, High (n=268, 259, 278, 163)
|
1 participants
|
0 participants
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Basophils, Low (n=269, 259, 278, 163)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Bilirubin Total, High (n=295, 290, 305, 168)
|
2 participants
|
4 participants
|
4 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Calcitonin, High (n=226, 233, 230, 113)
|
1 participants
|
2 participants
|
2 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Chloride, High (n=299, 293, 310, 174)
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Chloride, Low (n=299, 293, 308, 174)
|
1 participants
|
2 participants
|
1 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
CPK, High (n=273, 262, 276, 156
|
29 participants
|
20 participants
|
30 participants
|
7 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Creatinine, High (n=294, 285, 303, 172)
|
7 participants
|
10 participants
|
5 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Creatinine Clearance, High (n=164, 186, 180, 107)
|
17 participants
|
28 participants
|
26 participants
|
25 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Creatinine Clearance, Low (n=292, 278,303,168)
|
11 participants
|
17 participants
|
12 participants
|
6 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Eosinophils, High (n=258, 256, 275, 157)
|
4 participants
|
11 participants
|
6 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Eosinophils, Low (n=269, 259, 278, 163)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Leukocyte Count, High (n=272, 265, 286, 165)
|
3 participants
|
6 participants
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Leukocyte Count, Low (n=272, 262, 280, 165)
|
2 participants
|
3 participants
|
4 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
GGT, High (n=234, 240, 245, 144)
|
9 participants
|
11 participants
|
23 participants
|
10 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Hematocrit, High (n=273, 265, 279, 161)
|
1 participants
|
1 participants
|
1 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Lipase, High (n=255, 248, 269, 147)
|
109 participants
|
92 participants
|
97 participants
|
37 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Monocytes, Low (n=265, 255, 274, 158)
|
6 participants
|
5 participants
|
8 participants
|
10 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Neutrophils, High (n=264, 255, 276, 161)
|
4 participants
|
5 participants
|
3 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Lymphocytes, High (n=249, 253, 269, 161)
|
5 participants
|
9 participants
|
6 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Neutrophils, Low (n=263, 251, 271, 162)
|
2 participants
|
1 participants
|
2 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Platelet Count, High (n=265, 260, 281, 160)
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Hematocrit, Low (n=256, 242, 259, 157)
|
13 participants
|
10 participants
|
6 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Hemoglobin, High (n=278, 271, 289, 164)
|
1 participants
|
1 participants
|
1 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Lymphocytes, Low (n=265, 258, 273, 159)
|
3 participants
|
3 participants
|
4 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
MCHC, High (n=274, 265, 280, 163)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Hemoglobin, Low (n=262, 249, 265, 162)
|
13 participants
|
16 participants
|
5 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
MCHC, Low (n=273, 263, 279, 163)
|
0 participants
|
2 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
MCV, High (n=261, 248, 263, 156)
|
19 participants
|
12 participants
|
14 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
MCV, Low (n=264, 252, 275, 162)
|
3 participants
|
2 participants
|
2 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Platelet Count, Low (n=262, 252, 269, 154)
|
2 participants
|
3 participants
|
6 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Potassium, High (n=297, 291, 307, 172)
|
7 participants
|
2 participants
|
5 participants
|
4 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Potassium, Low (n=298, 293, 308, 169)
|
4 participants
|
6 participants
|
3 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Sodium, High (n=291, 291, 307, 170)
|
3 participants
|
4 participants
|
4 participants
|
4 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Sodium, Low (n=298, 292, 305, 174)
|
2 participants
|
1 participants
|
4 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Urea Nitrogen, High (n=287, 282, 305, 169)
|
11 participants
|
17 participants
|
13 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
UMCR, High (n=217, 204, 232, 130)
|
18 participants
|
9 participants
|
13 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Monocytes, High (n=266, 258, 274, 163)
|
1 participants
|
0 participants
|
3 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Erythrocyte Count, High (n=279, 272, 287, 164)
|
1 participants
|
1 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks
Erythrocyte Count, Low (n=274, 268, 280, 161)
|
12 participants
|
7 participants
|
7 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 52 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms with baseline value not in the specified direction of treatment-emergent abnormality and at least 1 postbaseline result.
The number of participants with treatment-emergent abnormal laboratory results (defined as abnormalities that first occur after baseline) was summarized cumulatively for alkaline phosphatase, alanine aminotransferase or serum glutamic pyruvic transaminase (ALT/SGPT), amylase (pancreatic and total), aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT), basophils, bilirubin (direct and total), calcitonin, chloride, creatine phosphokinase (CPK), creatinine, creatinine clearance, eosinophils, erythrocytes, gamma glutamyltransferase (GGT), hematocrit, hemoglobin, leukocytes, lipase, lymphocytes, mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), monocytes, neutrophils, platelets, potassium, sodium, urea nitrogen, and urine microalbumin-to-creatinine ratio (UMCR) .
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Alkaline Phosphatase, High (n=276, 258, 281)
|
10 participants
|
6 participants
|
16 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
ALT/SGPT, High (n=232, 237, 244)
|
25 participants
|
27 participants
|
28 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Amylase Pancreatic, High (n=283, 277, 295)
|
67 participants
|
70 participants
|
55 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Amylase Total, High (n=266, 265, 277)
|
38 participants
|
42 participants
|
36 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
AST/SGOT, High (n=273, 269, 284)
|
15 participants
|
19 participants
|
25 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Basophils, High (n=276, 268, 287)
|
1 participants
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Basophils, Low (n=277, 268, 287)
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Bilirubin Direct, High (n=295, 291, 307)
|
1 participants
|
1 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Bilirubin Total, High (n=295, 290, 305)
|
2 participants
|
6 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Calcitonin, High (n=233, 239, 235)
|
4 participants
|
2 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Chloride, High (n=299, 293, 310)
|
0 participants
|
1 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Chloride, Low (n=299, 293, 308)
|
1 participants
|
2 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
CPK, High (n=273, 262, 276)
|
38 participants
|
28 participants
|
43 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Creatinine, High (n=294, 285, 303)
|
9 participants
|
10 participants
|
6 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Creatinine Clearance, High (n=164, 186, 180)
|
23 participants
|
30 participants
|
29 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Creatinine Clearance, Low (n=292, 278, 303)
|
18 participants
|
20 participants
|
15 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Eosinophils, High (n=265, 265, 283)
|
11 participants
|
14 participants
|
10 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Eosinophils, Low (n=277, 268, 287)
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Erythrocyte Count, High (n=283, 276, 292)
|
3 participants
|
1 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Erythrocyte Count, Low (n=278, 272, 285)
|
15 participants
|
9 participants
|
11 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
GGT, High (n=234, 240, 245)
|
10 participants
|
14 participants
|
34 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Hematocrit, High (n=280, 274, 290)
|
3 participants
|
2 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Hematocrit, Low (n=262, 251, 269)
|
21 participants
|
13 participants
|
11 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Hemoglobin, High (n=282, 275, 294)
|
3 participants
|
1 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Hemoglobin, Low (n=265, 253, 269)
|
21 participants
|
19 participants
|
11 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Leukocyte Count, High (n=277, 270, 292)
|
7 participants
|
6 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Leukocyte Count, Low (n=277, 267, 284)
|
5 participants
|
3 participants
|
9 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Lipase, High (n=255, 248, 269)
|
124 participants
|
111 participants
|
110 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Lymphocytes, High (n=257, 262, 278)
|
12 participants
|
15 participants
|
11 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Lymphocytes, Low (n=273, 266, 280)
|
4 participants
|
4 participants
|
11 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
MCHC, High (n=281, 274, 291)
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
MCHC, Low (n=280, 272, 290)
|
2 participants
|
3 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
MCV, High (n=267, 256, 273)
|
25 participants
|
18 participants
|
19 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
MCV, Low (n=270, 261, 286)
|
3 participants
|
2 participants
|
4 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Monocytes, High (n=274, 267, 283)
|
1 participants
|
0 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Monocytes, Low (n=271, 264, 282)
|
8 participants
|
9 participants
|
15 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Neutrophils, High (n=272, 263, 285)
|
8 participants
|
7 participants
|
7 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Neutrophils, Low (n=271, 260, 279)
|
6 participants
|
2 participants
|
6 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Platelet Count, High (n=272, 267, 287)
|
0 participants
|
2 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Platelet Count, Low (n=269, 259, 275)
|
4 participants
|
5 participants
|
8 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Potassium, High (n=297, 291, 307)
|
10 participants
|
5 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Potassium, Low (n=298, 293, 308)
|
6 participants
|
7 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Sodium, High (n=291, 291, 307)
|
5 participants
|
8 participants
|
4 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Sodium, Low (n=298, 292, 305)
|
3 participants
|
1 participants
|
4 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
Urea Nitrogen, High (n=287, 282, 305)
|
14 participants
|
19 participants
|
21 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks
UMCR, High (n=223, 212, 238)
|
33 participants
|
21 participants
|
18 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms with baseline value not in the specified direction of treatment-emergent abnormality and at least 1 postbaseline result.
The number of participants with treatment-emergent abnormal laboratory results (defined as abnormalities that first occur after baseline) was summarized cumulatively for alkaline phosphatase, alanine aminotransferase or serum glutamic pyruvic transaminase (ALT/SGPT), amylase (pancreatic and total), aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT), basophils, bilirubin (direct and total), calcitonin, chloride, creatine phosphokinase (CPK), creatinine, creatinine clearance, eosinophils, erythrocytes, gamma glutamyltransferase (GGT), hematocrit, hemoglobin, leukocytes, lipase, lymphocytes, mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), monocytes, neutrophils, platelets, potassium, sodium, urea nitrogen, and urine microalbumin-to-creatinine ratio (UMCR).
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Sodium, Low (n=298, 292, 305)
|
5 participants
|
1 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Urea Nitrogen, High (n=287, 282, 305)
|
17 participants
|
29 participants
|
29 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Alkaline Phosphate, High (n=276, 258, 281)
|
13 participants
|
11 participants
|
20 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
ALT/SGPT, High (n=232, 237, 244)
|
29 participants
|
37 participants
|
39 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Amylase Pancreatic, High (n=283, 277, 295)
|
81 participants
|
78 participants
|
61 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Amylase Total, High (n=266, 265, 277)
|
44 participants
|
55 participants
|
43 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
AST/SGOT, High (n=273, 269, 284)
|
21 participants
|
27 participants
|
36 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Basophils, High (n=276, 268, 288)
|
1 participants
|
0 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Basophils, Low (n=277, 268, 288)
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Bilirubin Direct, High (n=295, 291, 307)
|
2 participants
|
1 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Bilirubin Total, High (n=295, 290, 305)
|
3 participants
|
8 participants
|
6 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Calcitonin, High (n=233, 239, 235)
|
5 participants
|
3 participants
|
4 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Chloride, High (n=299, 293, 310)
|
0 participants
|
2 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Chloride, Low (n=299, 293, 308)
|
3 participants
|
2 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
CPK, High (n=273, 262, 276)
|
52 participants
|
41 participants
|
54 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Creatinine, High (n=294, 285, 303)
|
11 participants
|
16 participants
|
9 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Creatinine Clearance, High (n=164, 186, 180)
|
26 participants
|
32 participants
|
34 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Creatinine Clearance, Low (n=292, 278, 303)
|
24 participants
|
25 participants
|
20 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Eosinophils, High (n=265, 265, 284)
|
12 participants
|
22 participants
|
14 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Eosinophils, Low (n=277, 268, 288)
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Erythrocyte Count, High (n=283, 276, 292)
|
3 participants
|
2 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Erythrocyte Count, Low (n=278, 272, 285)
|
18 participants
|
14 participants
|
19 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
GGT, High (n=234, 240, 245)
|
16 participants
|
24 participants
|
45 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Hematocrit, High (n=280, 274, 290)
|
3 participants
|
6 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Hematocrit, Low (n=262, 251, 269)
|
30 participants
|
24 participants
|
29 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Hemoglobin, High (n=282, 275, 294)
|
4 participants
|
3 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Hemoglobin, Low (n=265, 253, 269)
|
30 participants
|
28 participants
|
25 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Leukocyte Count, High (n=277, 270, 292)
|
13 participants
|
9 participants
|
8 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Leukocyte Count, Low (n=277, 267, 284)
|
9 participants
|
7 participants
|
14 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Lipase, High (n=255, 248, 269)
|
142 participants
|
132 participants
|
126 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Lymphocytes, High (n=257, 262, 279)
|
19 participants
|
20 participants
|
21 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Lymphocytes, Low (n=273, 266, 281)
|
5 participants
|
9 participants
|
12 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
MCHC, High (n=281, 274, 291)
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
MCHC, Low (n=280, 272, 290)
|
5 participants
|
4 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
MCV, High (n=267, 256, 273)
|
39 participants
|
25 participants
|
25 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
MCV, Low (n=270, 261, 286)
|
9 participants
|
3 participants
|
4 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Monocytes, High (n=274, 267, 284)
|
3 participants
|
1 participants
|
11 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Monocytes, Low (n=271, 264, 283)
|
10 participants
|
14 participants
|
17 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Neutrophils, High (n=272, 263, 286)
|
15 participants
|
12 participants
|
13 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Neutrophils, Low (n=271, 260, 280)
|
10 participants
|
6 participants
|
10 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Platelet Count, High (n=273, 268, 287)
|
2 participants
|
3 participants
|
3 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Platelet Count, Low (n=270, 260, 275)
|
8 participants
|
7 participants
|
8 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Potassium, High (n=297, 291, 307)
|
14 participants
|
9 participants
|
8 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Potassium, Low (n=298, 293, 308)
|
8 participants
|
8 participants
|
5 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
Sodium, High (n=291, 291, 307)
|
10 participants
|
10 participants
|
6 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks
UMCR, High (n=223, 212, 239)
|
38 participants
|
27 participants
|
30 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 26 and 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms with baseline value not in the specified direction of treatment-emergent abnormality and at least 1 postbaseline result.
The number of participants with treatment-emergent abnormal lipid test (cholesterol, high density lipoprotein cholesterol \[HDL-C\], low density lipoprotein cholesterol \[LDL-C\], and triglycerides \[TG\]) results (defined as lipid test abnormalities that first occurred after baseline) is summarized cumulatively.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Abnormal Lipid Tests
Cholesterol, High, 26 Weeks (n=144, 158, 139, 58)
|
16 participants
|
21 participants
|
20 participants
|
8 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Lipid Tests
Cholesterol, High, 104 Weeks (n=151, 164, 146)
|
34 participants
|
29 participants
|
34 participants
|
NA participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Lipid Tests
HDL-C, High, 26 Weeks (n=197, 201, 189, 78)
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Lipid Tests
HDL-C, Low, 26 Weeks (n=127, 137, 129, 52)
|
9 participants
|
13 participants
|
8 participants
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Lipid Tests
HDL-C, High, 104 Weeks (n=206, 212, 199)
|
2 participants
|
1 participants
|
2 participants
|
NA participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Lipid Tests
HDL-C, Low, 104 Weeks (n=134, 143, 138)
|
13 participants
|
20 participants
|
13 participants
|
NA participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Lipid Tests
LDL-C, High, 26 Weeks (n=155, 163, 150, 61)
|
15 participants
|
11 participants
|
19 participants
|
7 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Lipid Tests
LDL-C, High, 104 Weeks (n=163, 170, 157)
|
31 participants
|
23 participants
|
29 participants
|
NA participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Lipid Tests
TG, High, 26 Weeks (n=163, 174, 156, 64)
|
6 participants
|
13 participants
|
10 participants
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Abnormal Lipid Tests
TG, High, 104 Weeks (n=170, 183, 166)
|
13 participants
|
22 participants
|
15 participants
|
NA participants
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 27.4 weeksPopulation: All participants randomized before the dose decision point who had evaluable sitting pulse rate data.
Sitting pulse rate was measured at the time that the dose decision was made (dose decision point). Change from baseline in pulse rate was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the decision point was 27.4 weeks.
Outcome measures
| Measure |
1.5 mg LY2189265
n=14 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=30 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=23 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=9 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
n=20 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
n=22 Participants
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
n=17 Participants
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
n=35 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
n=33 Participants
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Pulse Rate at Dose Decision Point
|
6.63 beats per minute (bpm)
Standard Deviation 7.28
|
3.43 beats per minute (bpm)
Standard Deviation 10.14
|
2.39 beats per minute (bpm)
Standard Deviation 7.88
|
3.34 beats per minute (bpm)
Standard Deviation 9.88
|
-1.63 beats per minute (bpm)
Standard Deviation 8.03
|
1.91 beats per minute (bpm)
Standard Deviation 6.18
|
1.05 beats per minute (bpm)
Standard Deviation 9.44
|
-0.16 beats per minute (bpm)
Standard Deviation 8.07
|
1.81 beats per minute (bpm)
Standard Deviation 7.90
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 27.4 weeksPopulation: All participants randomized before the dose decision point who had evaluable sitting SBP and DBP data.
Sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at the dose decision point. Change from baseline in DBP was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the time of the decision point was 27.4 weeks.
Outcome measures
| Measure |
1.5 mg LY2189265
n=14 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=30 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=23 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=9 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
n=20 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
n=22 Participants
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
n=17 Participants
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
n=35 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
n=33 Participants
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Blood Pressure at Dose Decision Point
Sitting SBP
|
-8.85 millimeters of mercury (mmHg)
Standard Deviation 12.92
|
-4.63 millimeters of mercury (mmHg)
Standard Deviation 15.28
|
-4.77 millimeters of mercury (mmHg)
Standard Deviation 11.37
|
-2.00 millimeters of mercury (mmHg)
Standard Deviation 9.94
|
-6.21 millimeters of mercury (mmHg)
Standard Deviation 19.13
|
0.40 millimeters of mercury (mmHg)
Standard Deviation 11.51
|
1.67 millimeters of mercury (mmHg)
Standard Deviation 10.18
|
-2.16 millimeters of mercury (mmHg)
Standard Deviation 10.62
|
-0.61 millimeters of mercury (mmHg)
Standard Deviation 14.75
|
—
|
|
Change From Baseline in Blood Pressure at Dose Decision Point
Sitting DBP
|
-1.21 millimeters of mercury (mmHg)
Standard Deviation 7.47
|
-1.17 millimeters of mercury (mmHg)
Standard Deviation 6.32
|
-1.20 millimeters of mercury (mmHg)
Standard Deviation 4.67
|
-0.08 millimeters of mercury (mmHg)
Standard Deviation 8.00
|
-3.18 millimeters of mercury (mmHg)
Standard Deviation 10.13
|
-0.75 millimeters of mercury (mmHg)
Standard Deviation 7.99
|
1.28 millimeters of mercury (mmHg)
Standard Deviation 4.06
|
-1.11 millimeters of mercury (mmHg)
Standard Deviation 6.65
|
-0.22 millimeters of mercury (mmHg)
Standard Deviation 7.94
|
—
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable pulse data. If there were no data after the date of randomization, the endpoint was considered missing.
Sitting and standing pulse rate were measured. Least squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Pulse Rate
Sitting, 26 Weeks (n=271, 278, 283, 138)
|
2.57 beats per minute (bpm)
Standard Error 0.47
|
1.90 beats per minute (bpm)
Standard Error 0.47
|
-0.11 beats per minute (bpm)
Standard Error 0.46
|
-0.22 beats per minute (bpm)
Standard Error 0.65
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Pulse Rate
Sitting, 104 Weeks (n=197, 192, 191)
|
2.28 beats per minute (bpm)
Standard Error 0.53
|
2.77 beats per minute (bpm)
Standard Error 0.54
|
-0.78 beats per minute (bpm)
Standard Error 0.53
|
NA beats per minute (bpm)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Pulse Rate
Standing, 26 Weeks (n=271, 277, 281, 138)
|
3.24 beats per minute (bpm)
Standard Error 0.52
|
2.00 beats per minute (bpm)
Standard Error 0.52
|
-0.24 beats per minute (bpm)
Standard Error 0.51
|
-0.17 beats per minute (bpm)
Standard Error 0.71
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Pulse Rate
Standing, 104 Weeks (n=197, 192, 191)
|
2.26 beats per minute (bpm)
Standard Error 0.63
|
2.50 beats per minute (bpm)
Standard Error 0.64
|
-1.06 beats per minute (bpm)
Standard Error 0.63
|
NA beats per minute (bpm)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable SBP and DBP data. If there were no data after the date of randomization, the endpoint was considered missing.
Sitting and standing systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Least squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Blood Pressure
Sitting DBP, 104 Weeks (n=197, 192, 191)
|
0.38 millimeters of mercury (mmHg)
Standard Error 0.52
|
1.40 millimeters of mercury (mmHg)
Standard Error 0.52
|
-0.36 millimeters of mercury (mmHg)
Standard Error 0.52
|
NA millimeters of mercury (mmHg)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Blood Pressure
Sitting SBP, 26 Weeks (n=271, 278, 283, 138)
|
-1.73 millimeters of mercury (mmHg)
Standard Error 0.67
|
-1.40 millimeters of mercury (mmHg)
Standard Error 0.67
|
-1.94 millimeters of mercury (mmHg)
Standard Error 0.66
|
1.12 millimeters of mercury (mmHg)
Standard Error 0.92
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Blood Pressure
Sitting SBP, 104 Weeks (n=197, 192, 191)
|
-0.07 millimeters of mercury (mmHg)
Standard Error 0.81
|
1.28 millimeters of mercury (mmHg)
Standard Error 0.82
|
0.02 millimeters of mercury (mmHg)
Standard Error 0.82
|
NA millimeters of mercury (mmHg)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Blood Pressure
Sitting DBP, 26 Weeks (n=271, 278, 283, 138)
|
-0.43 millimeters of mercury (mmHg)
Standard Error 0.43
|
-0.20 millimeters of mercury (mmHg)
Standard Error 0.43
|
-1.06 millimeters of mercury (mmHg)
Standard Error 0.42
|
0.68 millimeters of mercury (mmHg)
Standard Error 0.58
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Blood Pressure
Standing SBP, 26 Weeks (n=271, 277, 281, 138)
|
-1.53 millimeters of mercury (mmHg)
Standard Error 0.76
|
-1.72 millimeters of mercury (mmHg)
Standard Error 0.76
|
-2.54 millimeters of mercury (mmHg)
Standard Error 0.74
|
0.26 millimeters of mercury (mmHg)
Standard Error 1.04
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Blood Pressure
Standing SBP, 104 Weeks (n=197, 192, 191)
|
-1.30 millimeters of mercury (mmHg)
Standard Error 0.92
|
0.17 millimeters of mercury (mmHg)
Standard Error 0.93
|
-1.20 millimeters of mercury (mmHg)
Standard Error 0.92
|
NA millimeters of mercury (mmHg)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Blood Pressure
Standing DBP, 26 Weeks (n=271, 277, 281, 138)
|
-0.11 millimeters of mercury (mmHg)
Standard Error 0.48
|
0.03 millimeters of mercury (mmHg)
Standard Error 0.48
|
-1.36 millimeters of mercury (mmHg)
Standard Error 0.47
|
-0.52 millimeters of mercury (mmHg)
Standard Error 0.66
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Blood Pressure
Standing DBP, 104 Weeks (n=197, 192, 191)
|
-0.23 millimeters of mercury (mmHg)
Standard Error 0.57
|
0.36 millimeters of mercury (mmHg)
Standard Error 0.58
|
-0.67 millimeters of mercury (mmHg)
Standard Error 0.58
|
NA millimeters of mercury (mmHg)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable ECG data. If there were no data after the date of randomization, the endpoint was considered missing.
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=177 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval
PR Interval, 26 Weeks (n=256, 261, 268, 132)
|
2.94 milliseconds (msec)
Standard Error 0.66
|
1.60 milliseconds (msec)
Standard Error 0.66
|
0.42 milliseconds (msec)
Standard Error 0.65
|
2.24 milliseconds (msec)
Standard Error 0.89
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval
PR Interval, 104 Weeks (n=168, 170, 167)
|
4.59 milliseconds (msec)
Standard Error 0.90
|
3.06 milliseconds (msec)
Standard Error 0.90
|
3.19 milliseconds (msec)
Standard Error 0.90
|
NA milliseconds (msec)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval
QTcF Interval, 26 Weeks (n=258, 262, 268, 132)
|
-3.86 milliseconds (msec)
Standard Error 0.75
|
-2.44 milliseconds (msec)
Standard Error 0.75
|
-1.31 milliseconds (msec)
Standard Error 0.73
|
1.76 milliseconds (msec)
Standard Error 1.02
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval
QTcF Interval, 104 Weeks (n=169, 170, 168)
|
-2.71 milliseconds (msec)
Standard Error 0.84
|
-2.49 milliseconds (msec)
Standard Error 0.84
|
-0.02 milliseconds (msec)
Standard Error 0.83
|
NA milliseconds (msec)
Standard Error NA
Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 52 weeks, and 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms who had evaluable IWQoL-Lite data. If there were no data after the date of randomization, the endpoint was considered missing.
The Impact of Weight on Quality of Life-Lite (IWQoL-Lite questionnaire) is an obesity-specific, 31-item questionnaire designed to measure the impact of weight on participants' quality of life. Items are scored on a 5-point numeric rating scale where 5 = "always true" and 1 = "never true". Items are summed into 6 scales (physical function \[11 items\], self-esteem \[7 items\], sexual life \[4 items\], public distress \[5 items\], work \[4 items\], and total score \[31 items\]) based on the average for the valid responses on that scale multiplied by the number of items on that scale (rounded to the nearest whole integer). Higher scores indicate lower levels of functioning (negative effects). Scores are linearly transformed to a 0 to 100 scale.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Participant-reported Outcomes, Impact of Weight on Quality of Life-Lite (IWQoL-Lite)
Total Score, Baseline (n=285, 284, 300)
|
83.41 units on a scale
Standard Deviation 16.031
|
82.55 units on a scale
Standard Deviation 16.952
|
83.97 units on a scale
Standard Deviation 16.514
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Participant-reported Outcomes, Impact of Weight on Quality of Life-Lite (IWQoL-Lite)
Total Score, 52 Weeks (n=237, 252, 247)
|
86.92 units on a scale
Standard Deviation 14.972
|
86.31 units on a scale
Standard Deviation 14.673
|
86.25 units on a scale
Standard Deviation 15.628
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Participant-reported Outcomes, Impact of Weight on Quality of Life-Lite (IWQoL-Lite)
Total Score, 104 Weeks (n=190, 190, 185)
|
88.08 units on a scale
Standard Deviation 15.555
|
87.47 units on a scale
Standard Deviation 15.183
|
86.93 units on a scale
Standard Deviation 16.304
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 52 weeks, and 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms who had evaluable EQ-5D data. If there were no data after the date of randomization, the endpoint was considered missing.
The EQ-5D questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts. The first part allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a three level scale of 1-3 (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). The second part of the questionnaire consists of a 100-millimeter visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health state).
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Participant-reported Outcomes, EQ-5D
VAS, 52 Weeks (n=238, 251, 245)
|
78.93 units on a scale
Standard Deviation 13.352
|
78.22 units on a scale
Standard Deviation 13.839
|
78.79 units on a scale
Standard Deviation 14.567
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Participant-reported Outcomes, EQ-5D
VAS, Baseline (n=285, 284, 301)
|
75.57 units on a scale
Standard Deviation 15.798
|
75.35 units on a scale
Standard Deviation 16.001
|
76.85 units on a scale
Standard Deviation 15.363
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Participant-reported Outcomes, EQ-5D
VAS, 104 Weeks (n=189, 190, 185)
|
79.66 units on a scale
Standard Deviation 13.820
|
78.52 units on a scale
Standard Deviation 14.114
|
81.34 units on a scale
Standard Deviation 13.708
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Participant-reported Outcomes, EQ-5D
EQ-5D, UK, Baseline (n=285, 281, 300)
|
0.80 units on a scale
Standard Deviation 0.222
|
0.82 units on a scale
Standard Deviation 0.223
|
0.84 units on a scale
Standard Deviation 0.216
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Participant-reported Outcomes, EQ-5D
EQ-5D, UK, 52 Weeks (n=237, 250, 244)
|
0.83 units on a scale
Standard Deviation 0.211
|
0.84 units on a scale
Standard Deviation 0.208
|
0.85 units on a scale
Standard Deviation 0.210
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Participant-reported Outcomes, EQ-5D
EQ-5D, UK, 104 Weeks (n=189, 190, 185)
|
0.84 units on a scale
Standard Deviation 0.203
|
0.86 units on a scale
Standard Deviation 0.184
|
0.86 units on a scale
Standard Deviation 0.198
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 52 and 104 weeksPopulation: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms.
The number of visits to the emergency room (ER) is summarized cumulatively.
Outcome measures
| Measure |
1.5 mg LY2189265
n=304 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Resource Utilization
52 Weeks
|
NA events
Data were not summarized cumulatively for this outcome measure.
|
NA events
Data were not summarized cumulatively for this outcome measure.
|
NA events
Data were not summarized cumulatively for this outcome measure.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Resource Utilization
104 Weeks
|
NA events
Data were not summarized cumulatively for this outcome measure.
|
NA events
Data were not summarized cumulatively for this outcome measure.
|
NA events
Data were not summarized cumulatively for this outcome measure.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 52 weeksPopulation: Randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) who had blood samples collected for PK assessments.
Pharmacokinetic (PK) parameter estimates from LY2189265 concentration data were obtained using a 2-compartment population PK model with first order absorption. Area under the plasma-concentration curve from 0 to 168 hours, steady state (AUC0-168h, ss) of LY2189265 is summarized.
Outcome measures
| Measure |
1.5 mg LY2189265
n=69 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=60 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Pharmacokinetics of LY2189265: Area Under the Concentration-Time Curve
|
13378 nanograms times hours per milliliter
Standard Deviation 6100
|
7246 nanograms times hours per milliliter
Standard Deviation 3304
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 104 weeksPopulation: All randomized participants in the LY2189265 arms who had evaluable ADA data. If there were no data after the date of randomization, the endpoint was considered missing.
The number of participants with postbaseline detection of treatment-emergent antidrug LY2189265 antibodies (ADA) is summarized.
Outcome measures
| Measure |
1.5 mg LY2189265
n=698 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Antibodies to LY2189265
|
9 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through 104 weeksPopulation: All randomized participants.
The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
1.5 mg LY2189265
n=15 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=30 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=304 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=10 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
n=25 Participants
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
n=24 Participants
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
n=177 Participants
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
n=177 Participants
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Adjudicated Pancreatitis at 104 Weeks
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
2 participants
|
0 participants
|
1 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through 104 weeksPopulation: All randomized participants.
Data on any new cardiovascular (CV) event was prospectively collected using a CV event electronic case report form. At prespecified visits, participants were asked about any new CV event. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs to be adjudicated include myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with adjudicated CV events is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
1.5 mg LY2189265
n=15 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.75 mg LY2189265
n=30 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Sitagliptin
n=304 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=10 Participants
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
n=302 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
0.5 mg LY2189265
n=25 Participants
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
n=24 Participants
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
n=315 Participants
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 26 Weeks)
n=177 Participants
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (26 Weeks Through 104 Weeks)
n=177 Participants
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Adjudicated Cardiovascular Events at 104 Weeks
Participants With Any CV Event
|
0 participants
|
0 participants
|
6 participants
|
0 participants
|
4 participants
|
0 participants
|
0 participants
|
5 participants
|
0 participants
|
3 participants
|
|
Number of Participants With Adjudicated Cardiovascular Events at 104 Weeks
Participants With a Fatal CV Event
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Adjudicated Cardiovascular Events at 104 Weeks
Participants With a Non-fatal CV Event
|
0 participants
|
0 participants
|
6 participants
|
0 participants
|
4 participants
|
0 participants
|
0 participants
|
4 participants
|
0 participants
|
2 participants
|
Adverse Events
3.0 mg LY2189265
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
2.0 mg LY2189265
Serious events: 1 serious events
Other events: 20 other events
Deaths: 0 deaths
1.5 mg LY2189265
Serious events: 36 serious events
Other events: 252 other events
Deaths: 0 deaths
1.0 mg LY2189265
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
0.75 mg LY2189265
Serious events: 23 serious events
Other events: 255 other events
Deaths: 0 deaths
0.5 mg LY2189265
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
0.25 mg LY2189265
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Sitagliptin
Serious events: 32 serious events
Other events: 239 other events
Deaths: 0 deaths
Placebo/Sitagliptin (Baseline Through 104 Weeks)
Serious events: 17 serious events
Other events: 138 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
3.0 mg LY2189265
n=15 participants at risk
LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)
|
2.0 mg LY2189265
n=30 participants at risk
LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)
|
1.5 mg LY2189265
n=304 participants at risk
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=10 participants at risk
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
n=302 participants at risk
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally, for 104 weeks
|
0.5 mg LY2189265
n=25 participants at risk
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
n=24 participants at risk
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
n=315 participants at risk
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 104 Weeks)
n=177 participants at risk
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily, for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Blood and lymphatic system disorders
Lymphadenitis
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/15
|
0.00%
0/30
|
0.66%
2/304 • Number of events 2
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Cardiac disorders
Mitral valve incompetence
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/15
|
0.00%
0/30
|
0.66%
2/304 • Number of events 2
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
1.1%
2/177 • Number of events 2
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Cardiac disorders
Prinzmetal angina
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Endocrine disorders
Goitre
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Eye disorders
Cataract
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.56%
1/177 • Number of events 1
|
|
Eye disorders
Retinal detachment
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Eye disorders
Retinal vein thrombosis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Gastrointestinal disorders
Femoral hernia, obstructive
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 2
|
0.00%
0/177
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
General disorders
Chest pain
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.63%
2/315 • Number of events 2
|
0.00%
0/177
|
|
General disorders
Injection site nodule
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/15
|
0.00%
0/30
|
0.66%
2/304 • Number of events 2
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
General disorders
Sudden death
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Infections and infestations
Appendicitis
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Infections and infestations
Cystitis
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Infections and infestations
Gastroenteritis
|
6.7%
1/15 • Number of events 1
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Infections and infestations
Injection site infection
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Infections and infestations
Kidney infection
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Infections and infestations
Localised infection
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Infections and infestations
Lung infection
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Infections and infestations
Pelvic inflammatory disease
|
0.00%
0/10
|
0.00%
0/22
|
0.63%
1/158 • Number of events 1
|
0.00%
0/7
|
0.00%
0/168
|
0.00%
0/12
|
0.00%
0/15
|
0.00%
0/164
|
0.00%
0/87
|
|
Infections and infestations
Pneumonia
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
4.0%
1/25 • Number of events 1
|
0.00%
0/24
|
0.63%
2/315 • Number of events 3
|
0.00%
0/177
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/15
|
0.00%
0/30
|
0.66%
2/304 • Number of events 2
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Infections and infestations
Septic shock
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Infections and infestations
Tubo-ovarian abscess
|
0.00%
0/10
|
0.00%
0/22
|
0.63%
1/158 • Number of events 1
|
0.00%
0/7
|
0.00%
0/168
|
0.00%
0/12
|
0.00%
0/15
|
0.00%
0/164
|
0.00%
0/87
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.66%
2/302 • Number of events 2
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Infections and infestations
Urosepsis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Injury, poisoning and procedural complications
Brain contusion
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Injury, poisoning and procedural complications
Epicondylitis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/15
|
0.00%
0/30
|
0.66%
2/304 • Number of events 2
|
0.00%
0/10
|
0.66%
2/302 • Number of events 2
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Forearm fracture
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Intervertebral disc injury
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Skull fracture
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Investigations
Blood calcitonin increased
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.99%
3/302 • Number of events 3
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Musculoskeletal and connective tissue disorders
Myofascial pain syndrome
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Musculoskeletal and connective tissue disorders
Myopathy
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.56%
1/177 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal cancer stage iii
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-secretory adenoma of pituitary
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal adenocarcinoma
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/5
|
0.00%
0/8
|
0.00%
0/146
|
0.00%
0/3
|
0.00%
0/134
|
0.00%
0/13
|
0.00%
0/9
|
0.66%
1/151 • Number of events 1
|
0.00%
0/90
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma
|
0.00%
0/5
|
0.00%
0/8
|
0.68%
1/146 • Number of events 1
|
0.00%
0/3
|
0.75%
1/134 • Number of events 1
|
0.00%
0/13
|
0.00%
0/9
|
0.00%
0/151
|
0.00%
0/90
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.00%
0/15
|
3.3%
1/30 • Number of events 1
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine cancer
|
0.00%
0/10
|
0.00%
0/22
|
0.00%
0/158
|
0.00%
0/7
|
0.00%
0/168
|
0.00%
0/12
|
0.00%
0/15
|
0.61%
1/164 • Number of events 1
|
0.00%
0/87
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/10
|
0.00%
0/22
|
0.63%
1/158 • Number of events 1
|
0.00%
0/7
|
0.00%
0/168
|
0.00%
0/12
|
0.00%
0/15
|
0.00%
0/164
|
0.00%
0/87
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Nervous system disorders
Coma
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Nervous system disorders
Demyelinating polyneuropathy
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Nervous system disorders
Intracranial aneurysm
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/15
|
0.00%
0/30
|
0.66%
2/304 • Number of events 2
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Renal and urinary disorders
Calculus urinary
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Renal and urinary disorders
Nephritis
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 2
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
0.00%
0/10
|
0.00%
0/22
|
0.00%
0/158
|
0.00%
0/7
|
0.00%
0/168
|
0.00%
0/12
|
0.00%
0/15
|
0.00%
0/164
|
1.1%
1/87 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 2
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Skin and subcutaneous tissue disorders
Diabetic foot
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Skin and subcutaneous tissue disorders
Stevens-johnson syndrome
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Surgical and medical procedures
Cholecystectomy
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Surgical and medical procedures
Spinal operation
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Vascular disorders
Haematoma
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.66%
2/302 • Number of events 2
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Vascular disorders
Varicose vein
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
Other adverse events
| Measure |
3.0 mg LY2189265
n=15 participants at risk
LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)
|
2.0 mg LY2189265
n=30 participants at risk
LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)
|
1.5 mg LY2189265
n=304 participants at risk
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
1.0 mg LY2189265
n=10 participants at risk
LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
0.75 mg LY2189265
n=302 participants at risk
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally, for 104 weeks
|
0.5 mg LY2189265
n=25 participants at risk
LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)
|
0.25 mg LY2189265
n=24 participants at risk
LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)
Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)
Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)
|
Sitagliptin
n=315 participants at risk
Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
Placebo/Sitagliptin (Baseline Through 104 Weeks)
n=177 participants at risk
Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks
Placebo: tablet, administered orally, once daily for 26 weeks
Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily, for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
|
|---|---|---|---|---|---|---|---|---|---|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/15
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/15
|
10.0%
3/30 • Number of events 3
|
3.3%
10/304 • Number of events 17
|
0.00%
0/10
|
0.99%
3/302 • Number of events 4
|
0.00%
0/25
|
4.2%
1/24 • Number of events 1
|
2.2%
7/315 • Number of events 7
|
0.56%
1/177 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/15
|
0.00%
0/30
|
4.3%
13/304 • Number of events 14
|
10.0%
1/10 • Number of events 1
|
5.0%
15/302 • Number of events 18
|
8.0%
2/25 • Number of events 2
|
0.00%
0/24
|
0.95%
3/315 • Number of events 3
|
0.56%
1/177 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
1/15 • Number of events 1
|
0.00%
0/30
|
6.9%
21/304 • Number of events 26
|
0.00%
0/10
|
4.3%
13/302 • Number of events 24
|
4.0%
1/25 • Number of events 1
|
0.00%
0/24
|
3.5%
11/315 • Number of events 12
|
2.3%
4/177 • Number of events 6
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/15
|
3.3%
1/30 • Number of events 1
|
4.6%
14/304 • Number of events 15
|
0.00%
0/10
|
4.0%
12/302 • Number of events 13
|
4.0%
1/25 • Number of events 1
|
0.00%
0/24
|
2.9%
9/315 • Number of events 10
|
5.6%
10/177 • Number of events 12
|
|
Gastrointestinal disorders
Constipation
|
6.7%
1/15 • Number of events 1
|
0.00%
0/30
|
4.6%
14/304 • Number of events 14
|
0.00%
0/10
|
5.3%
16/302 • Number of events 22
|
12.0%
3/25 • Number of events 3
|
0.00%
0/24
|
1.3%
4/315 • Number of events 4
|
0.56%
1/177 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/15
|
16.7%
5/30 • Number of events 5
|
16.4%
50/304 • Number of events 74
|
10.0%
1/10 • Number of events 1
|
11.9%
36/302 • Number of events 53
|
16.0%
4/25 • Number of events 5
|
8.3%
2/24 • Number of events 2
|
5.7%
18/315 • Number of events 30
|
8.5%
15/177 • Number of events 23
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/15
|
3.3%
1/30 • Number of events 1
|
5.9%
18/304 • Number of events 25
|
10.0%
1/10 • Number of events 1
|
6.3%
19/302 • Number of events 23
|
12.0%
3/25 • Number of events 4
|
4.2%
1/24 • Number of events 1
|
5.1%
16/315 • Number of events 17
|
2.3%
4/177 • Number of events 4
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/15
|
6.7%
2/30 • Number of events 2
|
1.3%
4/304 • Number of events 9
|
0.00%
0/10
|
0.33%
1/302 • Number of events 1
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Gastrointestinal disorders
Flatulence
|
6.7%
1/15 • Number of events 1
|
6.7%
2/30 • Number of events 2
|
2.3%
7/304 • Number of events 9
|
0.00%
0/10
|
1.7%
5/302 • Number of events 6
|
0.00%
0/25
|
0.00%
0/24
|
0.95%
3/315 • Number of events 3
|
0.56%
1/177 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/15
|
3.3%
1/30 • Number of events 1
|
3.6%
11/304 • Number of events 12
|
20.0%
2/10 • Number of events 3
|
1.3%
4/302 • Number of events 4
|
0.00%
0/25
|
0.00%
0/24
|
2.9%
9/315 • Number of events 9
|
4.0%
7/177 • Number of events 8
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.7%
1/15 • Number of events 1
|
3.3%
1/30 • Number of events 1
|
2.3%
7/304 • Number of events 8
|
0.00%
0/10
|
2.6%
8/302 • Number of events 8
|
0.00%
0/25
|
0.00%
0/24
|
2.2%
7/315 • Number of events 7
|
1.7%
3/177 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
33.3%
5/15 • Number of events 6
|
20.0%
6/30 • Number of events 6
|
17.4%
53/304 • Number of events 98
|
40.0%
4/10 • Number of events 5
|
14.6%
44/302 • Number of events 62
|
12.0%
3/25 • Number of events 6
|
8.3%
2/24 • Number of events 3
|
7.0%
22/315 • Number of events 27
|
5.1%
9/177 • Number of events 15
|
|
Gastrointestinal disorders
Vomiting
|
13.3%
2/15 • Number of events 2
|
13.3%
4/30 • Number of events 6
|
13.5%
41/304 • Number of events 62
|
20.0%
2/10 • Number of events 2
|
8.3%
25/302 • Number of events 43
|
4.0%
1/25 • Number of events 1
|
4.2%
1/24 • Number of events 2
|
3.5%
11/315 • Number of events 11
|
1.7%
3/177 • Number of events 3
|
|
General disorders
Asthenia
|
0.00%
0/15
|
6.7%
2/30 • Number of events 3
|
2.3%
7/304 • Number of events 8
|
0.00%
0/10
|
2.0%
6/302 • Number of events 6
|
0.00%
0/25
|
0.00%
0/24
|
1.6%
5/315 • Number of events 5
|
1.1%
2/177 • Number of events 2
|
|
General disorders
Chills
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
10.0%
1/10 • Number of events 1
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
General disorders
Fatigue
|
0.00%
0/15
|
0.00%
0/30
|
4.3%
13/304 • Number of events 15
|
10.0%
1/10 • Number of events 1
|
3.0%
9/302 • Number of events 9
|
0.00%
0/25
|
8.3%
2/24 • Number of events 2
|
3.5%
11/315 • Number of events 11
|
3.4%
6/177 • Number of events 6
|
|
General disorders
Temperature intolerance
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
10.0%
1/10 • Number of events 1
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Infections and infestations
Gastroenteritis
|
13.3%
2/15 • Number of events 2
|
0.00%
0/30
|
3.9%
12/304 • Number of events 12
|
0.00%
0/10
|
2.3%
7/302 • Number of events 10
|
4.0%
1/25 • Number of events 1
|
0.00%
0/24
|
1.9%
6/315 • Number of events 6
|
4.0%
7/177 • Number of events 8
|
|
Infections and infestations
Influenza
|
0.00%
0/15
|
3.3%
1/30 • Number of events 2
|
5.3%
16/304 • Number of events 19
|
0.00%
0/10
|
6.0%
18/302 • Number of events 22
|
0.00%
0/25
|
0.00%
0/24
|
4.4%
14/315 • Number of events 15
|
2.8%
5/177 • Number of events 5
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/15
|
3.3%
1/30 • Number of events 1
|
14.1%
43/304 • Number of events 64
|
0.00%
0/10
|
15.9%
48/302 • Number of events 96
|
4.0%
1/25 • Number of events 1
|
0.00%
0/24
|
14.9%
47/315 • Number of events 72
|
14.1%
25/177 • Number of events 44
|
|
Infections and infestations
Sinusitis
|
0.00%
0/15
|
3.3%
1/30 • Number of events 1
|
4.9%
15/304 • Number of events 22
|
0.00%
0/10
|
3.3%
10/302 • Number of events 14
|
8.0%
2/25 • Number of events 2
|
0.00%
0/24
|
2.2%
7/315 • Number of events 7
|
1.7%
3/177 • Number of events 3
|
|
Infections and infestations
Upper respiratory tract infection
|
6.7%
1/15 • Number of events 1
|
0.00%
0/30
|
7.2%
22/304 • Number of events 34
|
0.00%
0/10
|
7.3%
22/302 • Number of events 30
|
4.0%
1/25 • Number of events 1
|
0.00%
0/24
|
6.7%
21/315 • Number of events 24
|
4.0%
7/177 • Number of events 8
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/15
|
6.7%
2/30 • Number of events 2
|
6.9%
21/304 • Number of events 26
|
0.00%
0/10
|
7.0%
21/302 • Number of events 25
|
4.0%
1/25 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
6.0%
19/315 • Number of events 22
|
7.9%
14/177 • Number of events 21
|
|
Investigations
Amylase increased
|
0.00%
0/15
|
0.00%
0/30
|
2.0%
6/304 • Number of events 11
|
10.0%
1/10 • Number of events 1
|
1.7%
5/302 • Number of events 9
|
4.0%
1/25 • Number of events 1
|
0.00%
0/24
|
1.9%
6/315 • Number of events 8
|
0.56%
1/177 • Number of events 1
|
|
Investigations
Blood calcitonin increased
|
0.00%
0/15
|
0.00%
0/30
|
0.66%
2/304 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.63%
2/315 • Number of events 3
|
0.56%
1/177 • Number of events 2
|
|
Investigations
Lipase increased
|
0.00%
0/15
|
0.00%
0/30
|
3.6%
11/304 • Number of events 14
|
0.00%
0/10
|
4.3%
13/302 • Number of events 21
|
8.0%
2/25 • Number of events 2
|
4.2%
1/24 • Number of events 1
|
4.8%
15/315 • Number of events 16
|
2.8%
5/177 • Number of events 9
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/15
|
10.0%
3/30 • Number of events 5
|
9.5%
29/304 • Number of events 31
|
10.0%
1/10 • Number of events 1
|
5.6%
17/302 • Number of events 23
|
8.0%
2/25 • Number of events 2
|
4.2%
1/24 • Number of events 1
|
3.5%
11/315 • Number of events 11
|
1.7%
3/177 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/15
|
0.00%
0/30
|
9.9%
30/304 • Number of events 30
|
0.00%
0/10
|
12.6%
38/302 • Number of events 38
|
0.00%
0/25
|
0.00%
0/24
|
15.6%
49/315 • Number of events 49
|
15.8%
28/177 • Number of events 28
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/15
|
0.00%
0/30
|
4.9%
15/304 • Number of events 19
|
0.00%
0/10
|
6.3%
19/302 • Number of events 22
|
0.00%
0/25
|
0.00%
0/24
|
4.4%
14/315 • Number of events 16
|
4.0%
7/177 • Number of events 11
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/15
|
0.00%
0/30
|
6.9%
21/304 • Number of events 28
|
0.00%
0/10
|
9.3%
28/302 • Number of events 32
|
8.0%
2/25 • Number of events 2
|
0.00%
0/24
|
6.0%
19/315 • Number of events 24
|
5.1%
9/177 • Number of events 9
|
|
Musculoskeletal and connective tissue disorders
Synovial cyst
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
10.0%
1/10 • Number of events 1
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.00%
0/177
|
|
Nervous system disorders
Dizziness
|
6.7%
1/15 • Number of events 1
|
6.7%
2/30 • Number of events 3
|
2.3%
7/304 • Number of events 8
|
0.00%
0/10
|
6.0%
18/302 • Number of events 20
|
0.00%
0/25
|
0.00%
0/24
|
4.4%
14/315 • Number of events 20
|
3.4%
6/177 • Number of events 6
|
|
Nervous system disorders
Headache
|
0.00%
0/15
|
3.3%
1/30 • Number of events 1
|
9.5%
29/304 • Number of events 53
|
0.00%
0/10
|
8.9%
27/302 • Number of events 76
|
4.0%
1/25 • Number of events 1
|
4.2%
1/24 • Number of events 3
|
8.3%
26/315 • Number of events 33
|
6.8%
12/177 • Number of events 17
|
|
Psychiatric disorders
Depression
|
0.00%
0/15
|
0.00%
0/30
|
2.3%
7/304 • Number of events 7
|
10.0%
1/10 • Number of events 1
|
1.3%
4/302 • Number of events 4
|
4.0%
1/25 • Number of events 1
|
0.00%
0/24
|
1.6%
5/315 • Number of events 5
|
0.56%
1/177 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/15
|
0.00%
0/30
|
2.3%
7/304 • Number of events 10
|
0.00%
0/10
|
1.3%
4/302 • Number of events 4
|
8.0%
2/25 • Number of events 2
|
0.00%
0/24
|
2.2%
7/315 • Number of events 8
|
1.1%
2/177 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
6.7%
1/15 • Number of events 1
|
0.00%
0/30
|
1.3%
4/304 • Number of events 4
|
0.00%
0/10
|
1.7%
5/302 • Number of events 6
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.00%
0/177
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/15
|
0.00%
0/30
|
6.2%
19/304 • Number of events 24
|
0.00%
0/10
|
3.6%
11/302 • Number of events 12
|
0.00%
0/25
|
0.00%
0/24
|
5.4%
17/315 • Number of events 26
|
3.4%
6/177 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
0.00%
0/15
|
0.00%
0/30
|
0.00%
0/304
|
10.0%
1/10 • Number of events 1
|
0.66%
2/302 • Number of events 3
|
0.00%
0/25
|
4.2%
1/24 • Number of events 1
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
|
Vascular disorders
Hypotension
|
6.7%
1/15 • Number of events 1
|
0.00%
0/30
|
0.00%
0/304
|
0.00%
0/10
|
0.99%
3/302 • Number of events 4
|
0.00%
0/25
|
0.00%
0/24
|
0.32%
1/315 • Number of events 1
|
0.56%
1/177 • Number of events 1
|
|
Vascular disorders
Venous insufficiency
|
6.7%
1/15 • Number of events 1
|
0.00%
0/30
|
0.33%
1/304 • Number of events 1
|
0.00%
0/10
|
0.00%
0/302
|
0.00%
0/25
|
0.00%
0/24
|
0.00%
0/315
|
0.56%
1/177 • Number of events 1
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60