Trial Outcomes & Findings for A Study in Adults With Type 1 Diabetes (NCT NCT01421147)
NCT ID: NCT01421147
Last Updated: 2014-10-09
Results Overview
HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline HbA1c, treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
536 participants
Primary outcome timeframe
Baseline, Endpoint (up to 24 weeks)
Results posted on
2014-10-09
Participant Flow
This study included a 24-week treatment period followed by a 28-week extension period.
Participant milestones
| Measure |
LY2963016 + Insulin Lispro
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Treatment Period
STARTED
|
269
|
267
|
|
Treatment Period
Received at Least 1 Dose of Study Drug
|
268
|
267
|
|
Treatment Period
COMPLETED
|
253
|
256
|
|
Treatment Period
NOT COMPLETED
|
16
|
11
|
|
Extension Period
STARTED
|
253
|
256
|
|
Extension Period
COMPLETED
|
245
|
245
|
|
Extension Period
NOT COMPLETED
|
8
|
11
|
Reasons for withdrawal
| Measure |
LY2963016 + Insulin Lispro
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Treatment Period
Adverse Event
|
2
|
3
|
|
Treatment Period
Lost to Follow-up
|
2
|
1
|
|
Treatment Period
Physician Decision
|
2
|
2
|
|
Treatment Period
Withdrawal by Subject
|
10
|
5
|
|
Extension Period
Adverse Event
|
0
|
2
|
|
Extension Period
Death
|
0
|
1
|
|
Extension Period
Lost to Follow-up
|
2
|
5
|
|
Extension Period
Physician Decision
|
1
|
0
|
|
Extension Period
Withdrawal by Subject
|
5
|
3
|
Baseline Characteristics
A Study in Adults With Type 1 Diabetes
Baseline characteristics by cohort
| Measure |
LY2963016 + Insulin Lispro
n=268 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=267 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Total
n=535 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.96 years
STANDARD_DEVIATION 13.65 • n=99 Participants
|
41.37 years
STANDARD_DEVIATION 13.25 • n=107 Participants
|
41.16 years
STANDARD_DEVIATION 13.44 • n=206 Participants
|
|
Sex: Female, Male
Female
|
113 Participants
n=99 Participants
|
112 Participants
n=107 Participants
|
225 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
155 Participants
n=99 Participants
|
155 Participants
n=107 Participants
|
310 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
21 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
177 Participants
n=99 Participants
|
170 Participants
n=107 Participants
|
347 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
80 Participants
n=99 Participants
|
87 Participants
n=107 Participants
|
167 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
11 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
49 Participants
n=99 Participants
|
51 Participants
n=107 Participants
|
100 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
197 Participants
n=99 Participants
|
201 Participants
n=107 Participants
|
398 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
99 participants
n=99 Participants
|
96 participants
n=107 Participants
|
195 participants
n=206 Participants
|
|
Region of Enrollment
Hungary
|
14 participants
n=99 Participants
|
16 participants
n=107 Participants
|
30 participants
n=206 Participants
|
|
Region of Enrollment
Mexico
|
17 participants
n=99 Participants
|
19 participants
n=107 Participants
|
36 participants
n=206 Participants
|
|
Region of Enrollment
Greece
|
15 participants
n=99 Participants
|
13 participants
n=107 Participants
|
28 participants
n=206 Participants
|
|
Region of Enrollment
Belgium
|
12 participants
n=99 Participants
|
11 participants
n=107 Participants
|
23 participants
n=206 Participants
|
|
Region of Enrollment
Poland
|
18 participants
n=99 Participants
|
17 participants
n=107 Participants
|
35 participants
n=206 Participants
|
|
Region of Enrollment
Romania
|
18 participants
n=99 Participants
|
16 participants
n=107 Participants
|
34 participants
n=206 Participants
|
|
Region of Enrollment
Germany
|
26 participants
n=99 Participants
|
28 participants
n=107 Participants
|
54 participants
n=206 Participants
|
|
Region of Enrollment
Japan
|
49 participants
n=99 Participants
|
51 participants
n=107 Participants
|
100 participants
n=206 Participants
|
|
Baseline Hemoglobin A1c (HbA1c)
|
7.75 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.13 • n=99 Participants
|
7.79 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.03 • n=107 Participants
|
7.77 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.08 • n=206 Participants
|
|
Time of Basal Insulin Injection
Daytime
|
51 participants
n=99 Participants
|
48 participants
n=107 Participants
|
99 participants
n=206 Participants
|
|
Time of Basal Insulin Injection
Evening/Bedtime
|
217 participants
n=99 Participants
|
219 participants
n=107 Participants
|
436 participants
n=206 Participants
|
|
Body Weight
|
75.80 kilograms (kg)
STANDARD_DEVIATION 16.76 • n=99 Participants
|
74.77 kilograms (kg)
STANDARD_DEVIATION 15.36 • n=107 Participants
|
75.29 kilograms (kg)
STANDARD_DEVIATION 16.07 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, Endpoint (up to 24 weeks)Population: All randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline HbA1c measurement. Last observation carried forward (LOCF) principle was used.
HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline HbA1c, treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=267 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=267 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Change From Baseline up to 24 Weeks in Hemoglobin A1c (HbA1c)
|
-0.352 percentage of glycosylated hemoglobin
Standard Error 0.053
|
-0.460 percentage of glycosylated hemoglobin
Standard Error 0.054
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks and 12 weeks and Endpoints (up to 24 weeks and up to 52 weeks)Population: All randomized participants who received at least 1 dose of study drug and were insulin antibody positive at baseline and had at least 1 post-baseline insulin antibody positive measurement. Last observation carried forward (LOCF) principle was used for Endpoints (up to 24 and up to 52 weeks).
Blood samples are collected from participants and percentage of insulin antibody binding was measured to determine the insulin antibody levels. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=40 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=47 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Change From Baseline in Insulin Antibody Levels
Change at 6 weeks (n=31, 38)
|
0.30 percentage of insulin antibody binding
Standard Error 0.33
|
-0.12 percentage of insulin antibody binding
Standard Error 0.33
|
|
Change From Baseline in Insulin Antibody Levels
Change at Endpoint, up to 52 weeks (n=40, 47)
|
0.87 percentage of insulin antibody binding
Standard Error 0.58
|
0.06 percentage of insulin antibody binding
Standard Error 0.56
|
|
Change From Baseline in Insulin Antibody Levels
Change at 12 weeks (n=27, 36)
|
0.02 percentage of insulin antibody binding
Standard Error 0.39
|
-0.38 percentage of insulin antibody binding
Standard Error 0.39
|
|
Change From Baseline in Insulin Antibody Levels
Change at Endpoint, up to 24 weeks (n=37, 47)
|
0.47 percentage of insulin antibody binding
Standard Error 0.45
|
0.09 percentage of insulin antibody binding
Standard Error 0.44
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks and 12 weeks and 24 weeks and 36 weeks and 52 weeks and Endpoint (up to 52 weeks)Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline HbA1c measurements. Last observation carried forward (LOCF) principle was used for Endpoint (up to 52 weeks).
HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline HbA1c, treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=267 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=267 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Change From Baseline in Hemoglobin A1c (HbA1c)
Change at 12 weeks (n=261, 262)
|
-0.359 percentage of glycosylated hemoglobin
Standard Error 0.049
|
-0.472 percentage of glycosylated hemoglobin
Standard Error 0.049
|
|
Change From Baseline in Hemoglobin A1c (HbA1c)
Change at 24 weeks (n=256, 258)
|
-0.383 percentage of glycosylated hemoglobin
Standard Error 0.053
|
-0.481 percentage of glycosylated hemoglobin
Standard Error 0.053
|
|
Change From Baseline in Hemoglobin A1c (HbA1c)
Change at 52 weeks (n=248, 246)
|
-0.302 percentage of glycosylated hemoglobin
Standard Error 0.059
|
-0.306 percentage of glycosylated hemoglobin
Standard Error 0.060
|
|
Change From Baseline in Hemoglobin A1c (HbA1c)
Change at Endpoint, up to 52 weeks (n=267, 267)
|
-0.256 percentage of glycosylated hemoglobin
Standard Error 0.057
|
-0.276 percentage of glycosylated hemoglobin
Standard Error 0.058
|
|
Change From Baseline in Hemoglobin A1c (HbA1c)
Change at 36 weeks (n=253, 254)
|
-0.349 percentage of glycosylated hemoglobin
Standard Error 0.056
|
-0.408 percentage of glycosylated hemoglobin
Standard Error 0.056
|
|
Change From Baseline in Hemoglobin A1c (HbA1c)
Change at 6 weeks (n=265, 265)
|
-0.369 percentage of glycosylated hemoglobin
Standard Error 0.038
|
-0.362 percentage of glycosylated hemoglobin
Standard Error 0.039
|
SECONDARY outcome
Timeframe: Baseline and Endpoints [up to 24 weeks (wk) and up to 52 weeks]Population: All randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline SMBG measurement. Last observation carried forward (LOCF) principle was used.
7-point SMBG measurements are completed at the following timepoints: Morning (AM) Pre-Meal, AM Post-Prandial (PP), Midday (MD) Pre-Meal, MD PP, Evening (EV) Pre-Meal, Bed Time and 0300 hours. PP glucose is measured 2 hours (hrs) after the start of the meal. Values for the 7-point SMBG profiles were averaged over the three 7-point SMBG profiles during 2-week period prior to each visit. If only 1 of the 3 days of data was collected, then the value of the 1 day was used. If only 2 of the 3 days of data were collected, then the average of the 2 days was used. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=266 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=265 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Baseline-MD Pre-Meal (n=266, 265)
|
7.86 millimoles per liter (mmol/L)
Standard Error 0.16
|
8.14 millimoles per liter (mmol/L)
Standard Error 0.16
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Baseline-MD 2 hrs PP (n=264, 264)
|
9.12 millimoles per liter (mmol/L)
Standard Error 0.18
|
8.81 millimoles per liter (mmol/L)
Standard Error 0.18
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Baseline-EV Pre-Meal (n=264, 264)
|
8.87 millimoles per liter (mmol/L)
Standard Error 0.19
|
8.82 millimoles per liter (mmol/L)
Standard Error 0.19
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 24 wk-MD Pre-Meal (n=266, 265)
|
7.81 millimoles per liter (mmol/L)
Standard Error 0.19
|
7.84 millimoles per liter (mmol/L)
Standard Error 0.20
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Baseline-Bed Time (n=266, 264)
|
9.26 millimoles per liter (mmol/L)
Standard Error 0.20
|
9.37 millimoles per liter (mmol/L)
Standard Error 0.20
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Baseline-0300 hrs (n=262, 257)
|
8.27 millimoles per liter (mmol/L)
Standard Error 0.18
|
8.37 millimoles per liter (mmol/L)
Standard Error 0.18
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 24 wk-AM Pre-Meal (n=266, 264)
|
7.98 millimoles per liter (mmol/L)
Standard Error 0.20
|
7.81 millimoles per liter (mmol/L)
Standard Error 0.20
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 24 wk-AM 2 hrs PP (n=263, 262)
|
8.75 millimoles per liter (mmol/L)
Standard Error 0.20
|
8.50 millimoles per liter (mmol/L)
Standard Error 0.21
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 24 wk-MD 2 hrs PP (n=264, 264)
|
8.50 millimoles per liter (mmol/L)
Standard Error 0.21
|
8.41 millimoles per liter (mmol/L)
Standard Error 0.21
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 24 wk-0300 hrs (n=262, 257)
|
7.93 millimoles per liter (mmol/L)
Standard Error 0.20
|
8.38 millimoles per liter (mmol/L)
Standard Error 0.20
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 24 wk-EV Pre-Meal (n=264, 264)
|
8.82 millimoles per liter (mmol/L)
Standard Error 0.21
|
8.61 millimoles per liter (mmol/L)
Standard Error 0.22
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 24 wk-Bed Time (n=266, 264)
|
8.61 millimoles per liter (mmol/L)
Standard Error 0.22
|
9.11 millimoles per liter (mmol/L)
Standard Error 0.22
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 52 wk- AM Pre-Meal (n=266, 264)
|
8.03 millimoles per liter (mmol/L)
Standard Error 0.20
|
8.29 millimoles per liter (mmol/L)
Standard Error 0.21
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 52 wk-AM 2 hrs PP (n=263, 262)
|
8.55 millimoles per liter (mmol/L)
Standard Error 0.21
|
8.88 millimoles per liter (mmol/L)
Standard Error 0.21
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 52 wk-MD Pre-Meal (n=266, 265)
|
7.96 millimoles per liter (mmol/L)
Standard Error 0.19
|
7.99 millimoles per liter (mmol/L)
Standard Error 0.19
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 52 wk-MD 2 hrs PP (n=264, 264)
|
8.61 millimoles per liter (mmol/L)
Standard Error 0.21
|
8.74 millimoles per liter (mmol/L)
Standard Error 0.21
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 52 wk-EV Pre-Meal (n=264, 264)
|
8.37 millimoles per liter (mmol/L)
Standard Error 0.21
|
8.38 millimoles per liter (mmol/L)
Standard Error 0.21
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 52 wk-Bed Time (n=266, 264)
|
8.57 millimoles per liter (mmol/L)
Standard Error 0.21
|
9.06 millimoles per liter (mmol/L)
Standard Error 0.21
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Endpoint, up to 52 wk-0300 hrs (n=262, 257)
|
8.22 millimoles per liter (mmol/L)
Standard Error 0.21
|
8.43 millimoles per liter (mmol/L)
Standard Error 0.22
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Baseline-AM Pre-Meal (n=266, 264)
|
8.37 millimoles per liter (mmol/L)
Standard Error 0.18
|
8.19 millimoles per liter (mmol/L)
Standard Error 0.18
|
|
7-Point Self-Monitored Blood Glucose (SMBG) Profiles
Baseline-AM 2 hrs PP (n=263, 262)
|
8.93 millimoles per liter (mmol/L)
Standard Error 0.19
|
9.41 millimoles per liter (mmol/L)
Standard Error 0.19
|
SECONDARY outcome
Timeframe: Baseline and Endpoints (up to 24 weeks and up 52 weeks)Population: All randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline fasting blood glucose measurement. Last observation carried forward (LOCF) principle was used.
Glycemic variability is the intra-participant standard deviation (SD) value of fasting blood glucose as measured by the actual morning premeal blood glucose value from the 7-point self-monitoring blood glucose (SMBG) profiles. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=264 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=259 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Glycemic Variability of Fasting Blood Glucose
Baseline
|
2.51 millimoles per liter (mmol/L)
Standard Error 0.12
|
2.68 millimoles per liter (mmol/L)
Standard Error 0.12
|
|
Glycemic Variability of Fasting Blood Glucose
Endpoint, up to 24 weeks
|
2.25 millimoles per liter (mmol/L)
Standard Error 0.14
|
2.29 millimoles per liter (mmol/L)
Standard Error 0.14
|
|
Glycemic Variability of Fasting Blood Glucose
Endpoint, up to 52 weeks
|
2.08 millimoles per liter (mmol/L)
Standard Error 0.13
|
2.34 millimoles per liter (mmol/L)
Standard Error 0.13
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks and 12 weeks and 18 weeks and Endpoints (up to 24 weeks and up to 52 weeks)Population: All randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline body weight measurement. Last observation carried forward (LOCF) principle was used for Endpoints (up to 24 weeks and up to 52 weeks).
Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=268 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=267 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Change From Baseline in Body Weight
Change at 18 weeks (n=258, 260)
|
0.72 kilogram (kg)
Standard Error 0.15
|
0.55 kilogram (kg)
Standard Error 0.15
|
|
Change From Baseline in Body Weight
Change at 6 weeks (n=265, 265)
|
0.45 kilogram (kg)
Standard Error 0.09
|
0.42 kilogram (kg)
Standard Error 0.09
|
|
Change From Baseline in Body Weight
Change at 12 weeks (n=261, 261)
|
0.59 kilogram (kg)
Standard Error 0.13
|
0.48 kilogram (kg)
Standard Error 0.13
|
|
Change From Baseline in Body Weight
Change at Endpoint, up to 24 weeks (n=268, 267)
|
0.66 kilogram (kg)
Standard Error 0.17
|
0.42 kilogram (kg)
Standard Error 0.17
|
|
Change From Baseline in Body Weight
Change at Endpoint, up to 52 weeks (n=268, 267)
|
0.93 kilogram (kg)
Standard Error 0.21
|
0.59 kilogram (kg)
Standard Error 0.21
|
SECONDARY outcome
Timeframe: Baseline and 24 weeks and Endpoint (up to 52 weeks)Population: All randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline ALBSS measurement. Last observation carried forward (LOCF) principle was used for Endpoint (up to 52 weeks).
ALBSS contains 33 items, with each item scored on a 5-point response scale: 0 (never) to 4 (almost always). Items are categorized in 2 domains: Behavior (or avoidance) Items 1 to 15 and Worry (or affect) Items 16 to 33. Behavior Total Score (TS) range is 0 to 60 and Worry TS range is 0 to 72. Higher scores on "Behavior" items (related to avoidance of hypoglycemia) reflect greater awareness and/or effort of the participant to prevent low blood sugar. Higher scores on "Worry" items (related to worries about low blood sugar and its consequences) reflect greater participant concern about having low blood sugar. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=265 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=263 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Adult Low Blood Sugar Survey (ALBSS)
Baseline-Behavior TS (n=265, 263)
|
13.63 units on a scale
Standard Error 0.54
|
12.99 units on a scale
Standard Error 0.54
|
|
Adult Low Blood Sugar Survey (ALBSS)
24 weeks-Behavior TS (n=255, 257)
|
12.73 units on a scale
Standard Error 0.66
|
12.53 units on a scale
Standard Error 0.66
|
|
Adult Low Blood Sugar Survey (ALBSS)
24 weeks-Worry TS (n=255, 258)
|
15.39 units on a scale
Standard Error 1.08
|
14.27 units on a scale
Standard Error 1.08
|
|
Adult Low Blood Sugar Survey (ALBSS)
Endpoint, up to 52 weeks-Behavior TS (n=265, 263)
|
13.19 units on a scale
Standard Error 0.62
|
13.03 units on a scale
Standard Error 0.62
|
|
Adult Low Blood Sugar Survey (ALBSS)
Baseline-Worry TS (n=265, 263)
|
16.01 units on a scale
Standard Error 0.83
|
14.81 units on a scale
Standard Error 0.83
|
|
Adult Low Blood Sugar Survey (ALBSS)
Endpoint, up to 52 weeks-Worry TS (n=265, 263)
|
15.18 units on a scale
Standard Error 1.03
|
14.93 units on a scale
Standard Error 1.05
|
SECONDARY outcome
Timeframe: Baseline and 24 weeks and Endpoint (up to 52 weeks)Population: All randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline ITSQ measurements. Last observation carried forward (LOCF) principle was used for Endpoint (up to 52 weeks).
ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. Items measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother), with lower scores reflecting better outcomes. Items divided into 5 domains: Inconvenience of Regimen \[(IR) 5 items: scores range 5-35\], Lifestyle Flexibility \[(LF) 3 items: scores range 3-21\], Glycemic Control \[(GC) 3 items: scores range 3-21\], Hypoglycemic Control \[(HC) 5 items: scores range 5-35\], Insulin Delivery Device \[(IDD) 6 items: scores range 6-42\]. ITSQ Total Overall Scores range from 22-154. Data presented are the transformed score on a scale of 0-100, where transformed score=100×\[(7-raw score)/6\]. Higher scores indicate better treatment satisfaction. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=264 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=262 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
IR-Endpoint, up to 52 weeks (n=264, 263)
|
79.50 units on a scale
Standard Error 1.60
|
80.44 units on a scale
Standard Error 1.62
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
LF-24 weeks (n=254, 258)
|
64.18 units on a scale
Standard Error 1.90
|
63.34 units on a scale
Standard Error 1.90
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
GC-24 weeks (n=254, 258)
|
72.99 units on a scale
Standard Error 1.62
|
71.73 units on a scale
Standard Error 1.62
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
GC-Endpoint, up to 52 weeks (n=264, 263)
|
70.15 units on a scale
Standard Error 1.67
|
69.24 units on a scale
Standard Error 1.69
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
HC-Baseline (n=264, 263)
|
70.20 units on a scale
Standard Error 1.15
|
70.81 units on a scale
Standard Error 1.15
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
HC-24 weeks (n=254, 258)
|
70.40 units on a scale
Standard Error 1.48
|
71.42 units on a scale
Standard Error 1.48
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
HC-Endpoint, up to 52 weeks (n=264, 263)
|
70.46 units on a scale
Standard Error 1.47
|
71.72 units on a scale
Standard Error 1.49
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
IDD-Baseline (n=262, 262)
|
75.22 units on a scale
Standard Error 1.20
|
76.75 units on a scale
Standard Error 1.20
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
IDD-24 weeks (n=252, 258)
|
79.77 units on a scale
Standard Error 1.42
|
79.36 units on a scale
Standard Error 1.42
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
IDD-Endpoint, up to 52 weeks (n=262, 262)
|
79.46 units on a scale
Standard Error 1.37
|
79.75 units on a scale
Standard Error 1.39
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
ITSQ Total-Baseline (n=264, 262)
|
70.80 units on a scale
Standard Error 0.99
|
71.39 units on a scale
Standard Error 1.00
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
ITSQ Total-24 weeks (n=253, 258)
|
74.46 units on a scale
Standard Error 1.23
|
74.23 units on a scale
Standard Error 1.24
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
ITSQ Total-Endpoint, up to 52 weeks (n=264, 262)
|
73.94 units on a scale
Standard Error 1.25
|
74.48 units on a scale
Standard Error 1.26
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
IR-Baseline (n=264, 263)
|
74.62 units on a scale
Standard Error 1.31
|
75.39 units on a scale
Standard Error 1.32
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
IR-24 weeks (n=254, 258)
|
79.32 units on a scale
Standard Error 1.62
|
78.76 units on a scale
Standard Error 1.62
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
LF-Baseline (n=264, 263)
|
63.19 units on a scale
Standard Error 1.47
|
62.38 units on a scale
Standard Error 1.47
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
LF-Endpoint, up to 52 weeks (n=264, 263)
|
63.25 units on a scale
Standard Error 1.86
|
64.16 units on a scale
Standard Error 1.88
|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
GC-Baseline (n=264, 263)
|
64.44 units on a scale
Standard Error 1.34
|
64.34 units on a scale
Standard Error 1.34
|
SECONDARY outcome
Timeframe: Endpoints [up to 24 weeks (wk) and up to 52 weeks]Population: All randomized participants who received at least 1 dose of study drug and had at least 1 daily insulin dose per body weight measurements. Last observation carried forward (LOCF) principle was used.
Total daily insulin dose was adjusted for body weight \[units of insulin/kilogram/day (U/kg/day)\]. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=268 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=266 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Insulin Dose Per Body Weight (U/kg) (Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 24 wk-Basal Insulin (n=268, 266)
|
0.371 U/kg/day
Standard Error 0.011
|
0.358 U/kg/day
Standard Error 0.011
|
|
Insulin Dose Per Body Weight (U/kg) (Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 24 wk-Bolus Insulin (n=264, 266)
|
0.352 U/kg/day
Standard Error 0.015
|
0.346 U/kg/day
Standard Error 0.016
|
|
Insulin Dose Per Body Weight (U/kg) (Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 24 wk-Total Insulin (n=264, 266)
|
0.723 U/kg/day
Standard Error 0.021
|
0.704 U/kg/day
Standard Error 0.021
|
|
Insulin Dose Per Body Weight (U/kg) (Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 52 wk-Basal Insulin (n=268, 266)
|
0.379 U/kg/day
Standard Error 0.012
|
0.361 U/kg/day
Standard Error 0.012
|
|
Insulin Dose Per Body Weight (U/kg) (Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 52 wk-Bolus Insulin (n=264, 266)
|
0.369 U/kg/day
Standard Error 0.016
|
0.370 U/kg/day
Standard Error 0.016
|
|
Insulin Dose Per Body Weight (U/kg) (Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 52 wk-Total Insulin (n=264, 266)
|
0.748 U/kg/day
Standard Error 0.022
|
0.731 U/kg/day
Standard Error 0.022
|
SECONDARY outcome
Timeframe: Endpoints [up to 24 weeks (wk) and up to 52 weeks]Population: All randomized participants who received at least 1 dose of study drug and had at least 1 insulin daily dose measurements. Last observation carried forward (LOCF) principle was used.
Units of insulin taken daily were presented. Least Squares (LS) means were calculated by analysis of covariance (ANCOVA) and adjusted for baseline hemoglobin A1c (HbA1c), treatment and time of basal insulin injection (daytime, evening/bedtime) and country.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=268 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=266 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Insulin Dose - Units [Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 24 wk-Bolus Insulin (n=264, 266)
|
26.337 units of insulin per day (U/day)
Standard Error 1.347
|
25.069 units of insulin per day (U/day)
Standard Error 1.362
|
|
Insulin Dose - Units [Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 24 wk-Basal Insulin (n=268, 266)
|
27.773 units of insulin per day (U/day)
Standard Error 0.970
|
26.049 units of insulin per day (U/day)
Standard Error 0.987
|
|
Insulin Dose - Units [Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 24 wk-Total Insulin (n=264, 266)
|
54.118 units of insulin per day (U/day)
Standard Error 1.948
|
51.154 units of insulin per day (U/day)
Standard Error 1.970
|
|
Insulin Dose - Units [Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 52 wk-Basal Insulin (n=268, 266)
|
28.463 units of insulin per day (U/day)
Standard Error 1.073
|
26.404 units of insulin per day (U/day)
Standard Error 1.091
|
|
Insulin Dose - Units [Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 52 wk-Bolus Insulin (n=264, 266)
|
27.800 units of insulin per day (U/day)
Standard Error 1.329
|
27.098 units of insulin per day (U/day)
Standard Error 1.344
|
|
Insulin Dose - Units [Total and by Component [Basal and Bolus (Lispro)])
Endpoint, up to 52 wk-Total Insulin (n=264, 266)
|
56.255 units of insulin per day (U/day)
Standard Error 2.008
|
53.454 units of insulin per day (U/day)
Standard Error 2.031
|
SECONDARY outcome
Timeframe: Baseline and 6 weeks and 12 weeks and 24 weeks and 36 weeks and 52 weeks and Endpoints (up to 24 weeks and up to 52 weeks)Population: All randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline HbA1c measurement. Last observation carried forward (LOCF) principle was used for Endpoints (up to 24 weeks and up to 52 weeks).
HbA1c is the glycosylated fraction of hemoglobin A which provides an estimate of a participant's blood sugar control over a 6- to 12-week period. The percentage of participants with Hemoglobin A1c (HbA1c) \<7.0% or HbA1c ≤6.5% is calculated as the number of participants with an HbA1c level of the cut-off value (\<7.0% or ≤6.5%) divided by the number of participants treated, then multiplied by 100.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=267 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=267 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at Baseline <7.0 % (n=267, 267)
|
28.8 percentage of participants
|
19.5 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at Baseline ≤6.5% (n=267, 267)
|
13.9 percentage of participants
|
12.0 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at 6 weeks <7.0% (n=265, 265)
|
37.0 percentage of participants
|
26.4 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at 6 weeks ≤6.5% (n=265, 265)
|
21.1 percentage of participants
|
14.3 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at 12 weeks <7.0% (n=261, 262)
|
33.3 percentage of participants
|
29.8 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at 12 weeks ≤6.5% (n=261, 262)
|
19.9 percentage of participants
|
15.3 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at 24 weeks <7.0% (n=256, 258)
|
34.0 percentage of participants
|
33.3 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at 24 weeks ≤6.5% (n=256, 258)
|
19.9 percentage of participants
|
19.0 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at 36 weeks <7.0% (n=253, 254)
|
32.0 percentage of participants
|
28.3 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at 36 weeks ≤6.5% (n=253, 254)
|
15.4 percentage of participants
|
18.5 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at 52 weeks <7.0% (n=248, 246)
|
29.8 percentage of participants
|
27.2 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- at 52 weeks ≤6.5% (n=248, 246)
|
15.3 percentage of participants
|
14.6 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- Endpoint, up to 24 weeks <7.0% (n=267, 267)
|
34.5 percentage of participants
|
32.2 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- Endpoint, up to 24 weeks ≤6.5% (n=267, 267)
|
20.2 percentage of participants
|
18.4 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- Endpoint, up to 52 weeks <7.0% (n=267, 267)
|
30.3 percentage of participants
|
25.1 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% and HbA1c ≤6.5%
HbA1c- Endpoint, up to 52 weeks ≤6.5% (n=267, 267)
|
15.7 percentage of participants
|
13.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through 24 weeks (wk) and 52 weeksPopulation: All randomized participants who received at least 1 dose of study drug.
Incidence of hypoglycemic events is defined as the number of hypoglycemic events. A hypoglycemic event is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has a blood glucose (BG) concentration of ≤ 70 milligrams/deciliter \[mg/dL (3.9 millimoles/liter (mmol/L)\], even if it was not associated with signs, symptoms, or treatment consistent with current guidelines \[American Diabetes Association (ADA) 2005\]. Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions (these episodes may be associated with sufficient neuroglycopenia to induce seizure or coma; also, BG measurements may not be available during such an event). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=268 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=267 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Incidence of Hypoglycemic Events
Nocturnal Events with BG ≤70 mg/dL-24 wk
|
2217 events
|
2249 events
|
|
Incidence of Hypoglycemic Events
Total Events with BG ≤70 mg/dL,if available-24 wk
|
10411 events
|
10976 events
|
|
Incidence of Hypoglycemic Events
Total Events with BG ≤70 mg/dL,if available-52-wk
|
19541 events
|
20852 events
|
|
Incidence of Hypoglycemic Events
Severe Events-24 wk
|
6 events
|
10 events
|
|
Incidence of Hypoglycemic Events
Severe Events-52 wk
|
13 events
|
16 events
|
|
Incidence of Hypoglycemic Events
Nocturnal Events with BG ≤70 mg/dL-52 wk
|
4105 events
|
4485 events
|
SECONDARY outcome
Timeframe: Baseline through 24 weeks (wk) and 52 weeksPopulation: All randomized participants who received at least 1 dose of study drug.
The rate of hypoglycemic events per 30 days is defined as the total number of events between visits divided by the actual number of days between visits, and then multiplied by 30 days. A hypoglycemic event is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose (BG) concentration of ≤ 70 milligrams/deciliter \[mg/dL (3.9 millimoles/liter (mmol/L)\], even if it was not associated with signs, symptoms, or treatment consistent with current guidelines (ADA 2005). Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions (these episodes may be associated with sufficient neuroglycopenia to induce seizure or coma; also, BG measurements may not be available during such an event). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking.
Outcome measures
| Measure |
LY2963016 + Insulin Lispro
n=268 Participants
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=267 Participants
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Rate Per 30 Days of Hypoglycemic Events
Severe Events-24 wk
|
0.00 hypoglycemic events per 30 days
Standard Deviation 0.04
|
0.01 hypoglycemic events per 30 days
Standard Deviation 0.04
|
|
Rate Per 30 Days of Hypoglycemic Events
Nocturnal Events with BG ≤70 mg/dL-24 wk
|
1.50 hypoglycemic events per 30 days
Standard Deviation 1.93
|
1.51 hypoglycemic events per 30 days
Standard Deviation 1.77
|
|
Rate Per 30 Days of Hypoglycemic Events
Total Events with BG ≤70 mg/dL, if available-24 wk
|
7.10 hypoglycemic events per 30 days
Standard Deviation 6.35
|
7.32 hypoglycemic events per 30 days
Standard Deviation 6.58
|
|
Rate Per 30 Days of Hypoglycemic Events
Total Events with BG ≤70 mg/dL, if available-52 wk
|
6.33 hypoglycemic events per 30 days
Standard Deviation 5.64
|
6.56 hypoglycemic events per 30 days
Standard Deviation 6.12
|
|
Rate Per 30 Days of Hypoglycemic Events
Severe Events-52 wk
|
0.01 hypoglycemic events per 30 days
Standard Deviation 0.04
|
0.01 hypoglycemic events per 30 days
Standard Deviation 0.04
|
|
Rate Per 30 Days of Hypoglycemic Events
Nocturnal Events with BG ≤70 mg/dL-52 wk
|
1.32 hypoglycemic events per 30 days
Standard Deviation 1.66
|
1.42 hypoglycemic events per 30 days
Standard Deviation 1.60
|
Adverse Events
LY2963016 + Insulin Lispro
Serious events: 20 serious events
Other events: 161 other events
Deaths: 0 deaths
Lantus + Insulin Lispro
Serious events: 24 serious events
Other events: 158 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LY2963016 + Insulin Lispro
n=268 participants at risk
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=267 participants at risk
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Cardiac disorders
Hypertrophic cardiomyopathy
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
General disorders
Chest pain
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
|
Infections and infestations
Acute tonsillitis
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Infections and infestations
Cellulitis
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
|
Infections and infestations
Gangrene
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Infections and infestations
Lung infection
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
|
Infections and infestations
Pneumonia bacterial
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Maternal exposure during pregnancy
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
4.9%
13/268 • Number of events 16
|
4.5%
12/267 • Number of events 17
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Exostosis of jaw
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gliomatosis cerebri
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Nervous system disorders
Convulsion
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Nervous system disorders
Trigeminal neuralgia
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Psychiatric disorders
Psychotic disorder
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
|
Psychiatric disorders
Suicidal ideation
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation
|
0.00%
0/268
|
0.37%
1/267 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.37%
1/268 • Number of events 1
|
0.00%
0/267
|
Other adverse events
| Measure |
LY2963016 + Insulin Lispro
n=268 participants at risk
LY2963016 dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
Lantus + Insulin Lispro
n=267 participants at risk
Lantus dose was titrated based on blood glucose readings, and administered subcutaneously, once daily at the same timing (daytime or evening/bedtime) as participant's prestudy basal insulin injection schedule in combination with premeal insulin lispro for 52 weeks. Insulin lispro dosing was titrated based on blood glucose readings, and administered subcutaneously, 3 times a day for 52 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.1%
3/268 • Number of events 3
|
1.9%
5/267 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhoea
|
4.5%
12/268 • Number of events 13
|
3.7%
10/267 • Number of events 16
|
|
Gastrointestinal disorders
Gastritis
|
1.1%
3/268 • Number of events 3
|
1.5%
4/267 • Number of events 4
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
1.5%
4/268 • Number of events 4
|
1.1%
3/267 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
0.37%
1/268 • Number of events 1
|
1.1%
3/267 • Number of events 4
|
|
Gastrointestinal disorders
Toothache
|
1.5%
4/268 • Number of events 5
|
0.37%
1/267 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
6/268 • Number of events 6
|
0.75%
2/267 • Number of events 2
|
|
General disorders
Fatigue
|
1.5%
4/268 • Number of events 4
|
1.1%
3/267 • Number of events 4
|
|
General disorders
Influenza like illness
|
1.1%
3/268 • Number of events 4
|
1.9%
5/267 • Number of events 6
|
|
General disorders
Injection site reaction
|
1.1%
3/268 • Number of events 17
|
0.75%
2/267 • Number of events 3
|
|
General disorders
Pyrexia
|
1.5%
4/268 • Number of events 4
|
0.00%
0/267
|
|
Immune system disorders
Seasonal allergy
|
1.1%
3/268 • Number of events 3
|
0.75%
2/267 • Number of events 2
|
|
Infections and infestations
Bronchitis
|
1.5%
4/268 • Number of events 4
|
3.0%
8/267 • Number of events 9
|
|
Infections and infestations
Cystitis
|
0.00%
0/268
|
1.1%
3/267 • Number of events 3
|
|
Infections and infestations
Gastroenteritis
|
3.0%
8/268 • Number of events 8
|
2.6%
7/267 • Number of events 7
|
|
Infections and infestations
Gastroenteritis viral
|
1.9%
5/268 • Number of events 6
|
1.1%
3/267 • Number of events 3
|
|
Infections and infestations
Influenza
|
1.9%
5/268 • Number of events 7
|
3.4%
9/267 • Number of events 9
|
|
Infections and infestations
Nasopharyngitis
|
16.0%
43/268 • Number of events 68
|
16.9%
45/267 • Number of events 58
|
|
Infections and infestations
Pharyngitis
|
1.1%
3/268 • Number of events 3
|
1.5%
4/267 • Number of events 4
|
|
Infections and infestations
Sinusitis
|
2.6%
7/268 • Number of events 8
|
3.0%
8/267 • Number of events 11
|
|
Infections and infestations
Tooth abscess
|
0.37%
1/268 • Number of events 1
|
1.5%
4/267 • Number of events 5
|
|
Infections and infestations
Upper respiratory tract infection
|
8.2%
22/268 • Number of events 24
|
7.9%
21/267 • Number of events 28
|
|
Infections and infestations
Urinary tract infection
|
1.5%
4/268 • Number of events 4
|
1.9%
5/267 • Number of events 5
|
|
Infections and infestations
Viral upper respiratory tract infection
|
1.1%
3/268 • Number of events 3
|
0.75%
2/267 • Number of events 3
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
1.1%
3/268 • Number of events 3
|
0.00%
0/267
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.1%
3/268 • Number of events 3
|
1.9%
5/267 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.7%
10/268 • Number of events 11
|
3.4%
9/267 • Number of events 9
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.75%
2/268 • Number of events 2
|
1.9%
5/267 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.75%
2/268 • Number of events 2
|
1.1%
3/267 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.1%
3/268 • Number of events 3
|
0.75%
2/267 • Number of events 3
|
|
Nervous system disorders
Dizziness
|
2.2%
6/268 • Number of events 7
|
0.00%
0/267
|
|
Nervous system disorders
Headache
|
2.6%
7/268 • Number of events 7
|
2.6%
7/267 • Number of events 17
|
|
Psychiatric disorders
Depression
|
1.1%
3/268 • Number of events 3
|
0.75%
2/267 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.2%
6/268 • Number of events 6
|
3.0%
8/267 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
1.1%
3/268 • Number of events 3
|
1.1%
3/267 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.9%
5/268 • Number of events 5
|
1.5%
4/267 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
2.2%
6/268 • Number of events 7
|
1.9%
5/267 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
1.5%
4/268 • Number of events 5
|
0.75%
2/267 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.75%
2/268 • Number of events 2
|
1.1%
3/267 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.37%
1/268 • Number of events 1
|
1.5%
4/267 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.1%
3/268 • Number of events 5
|
0.37%
1/267 • Number of events 1
|
|
Vascular disorders
Hypertension
|
3.4%
9/268 • Number of events 9
|
1.9%
5/267 • Number of events 5
|
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