Trial Outcomes & Findings for A Study Comparing Dulaglutide With Insulin Glargine on Glycemic Control in Participants With Type 2 Diabetes (T2D) and Moderate or Severe Chronic Kidney Disease (CKD) (NCT NCT01621178)

Last Updated: 2019-09-19

Results Overview

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) means in HbA1c were calculated using a restricted maximum likelihood (REML) based mixed-effects model for repeated measures (MMRM) with the change in HbA1c as the dependent variable and treatment, macroalbuminuria (MA) region, Baseline CKD Severity, week, treatment\*week, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

577 participants

Primary outcome timeframe

Baseline, 26 Weeks

Results posted on

2019-09-19

Participant Flow

This was a parallel-arm, non-inferiority study. Study treatment continued for up to 52 weeks and participants were randomized in a 1:1:1 ratio to one of the 3 treatment arms: 1.5 milligrams (mg) dulaglutide once-weekly , 0.75 mg dulaglutide once-weekly, or insulin glargine once-daily.

Participant milestones

Participant milestones
Measure	Insulin Glargine Insulin glargine was administered subcutaneously (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	0.75 mg Dulaglutide 0.75 milligram (mg) of dulaglutide was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	1.5 mg Dulaglutide 1.5 mg of dulaglutide was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Overall Study STARTED	194	190	193
Overall Study Received at Least One Dose of Study Drug	194	190	192
Overall Study Modified Intent to Treat Population	186	180	183
Overall Study COMPLETED	163	160	157
Overall Study NOT COMPLETED	31	30	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Glargine Insulin glargine was administered subcutaneously (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	0.75 mg Dulaglutide 0.75 milligram (mg) of dulaglutide was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	1.5 mg Dulaglutide 1.5 mg of dulaglutide was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Overall Study Adverse Event	5	2	8
Overall Study Death	6	7	2
Overall Study Lost to Follow-up	1	2	1
Overall Study Withdrawal by Subject	14	17	18
Overall Study Physician Decision	5	2	7

Baseline Characteristics

A Study Comparing Dulaglutide With Insulin Glargine on Glycemic Control in Participants With Type 2 Diabetes (T2D) and Moderate or Severe Chronic Kidney Disease (CKD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Glargine n=194 Participants Insulin glargine was administered SC at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=190 Participants Dulaglutide 0.75 mg administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=192 Participants Dulaglutide 1.5 mg administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Total n=576 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 8.41 • n=99 Participants	64.7 years STANDARD_DEVIATION 8.61 • n=107 Participants	64.7 years STANDARD_DEVIATION 8.83 • n=206 Participants	64.6 years STANDARD_DEVIATION 8.60 • n=7 Participants
Sex: Female, Male Female	101 Participants n=99 Participants	86 Participants n=107 Participants	88 Participants n=206 Participants	275 Participants n=7 Participants
Sex: Female, Male Male	93 Participants n=99 Participants	104 Participants n=107 Participants	104 Participants n=206 Participants	301 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	79 Participants n=99 Participants	75 Participants n=107 Participants	78 Participants n=206 Participants	232 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	115 Participants n=99 Participants	115 Participants n=107 Participants	114 Participants n=206 Participants	344 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	18 Participants n=99 Participants	17 Participants n=107 Participants	12 Participants n=206 Participants	47 Participants n=7 Participants
Race (NIH/OMB) Asian	5 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants	16 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) Black or African American	26 Participants n=99 Participants	36 Participants n=107 Participants	26 Participants n=206 Participants	88 Participants n=7 Participants
Race (NIH/OMB) White	137 Participants n=99 Participants	122 Participants n=107 Participants	134 Participants n=206 Participants	393 Participants n=7 Participants
Race (NIH/OMB) More than one race	6 Participants n=99 Participants	7 Participants n=107 Participants	10 Participants n=206 Participants	23 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	4 Participants n=107 Participants	3 Participants n=206 Participants	8 Participants n=7 Participants
Region of Enrollment Romania	14 Participants n=99 Participants	9 Participants n=107 Participants	14 Participants n=206 Participants	37 Participants n=7 Participants
Region of Enrollment Hungary	22 Participants n=99 Participants	19 Participants n=107 Participants	14 Participants n=206 Participants	55 Participants n=7 Participants
Region of Enrollment United States	61 Participants n=99 Participants	59 Participants n=107 Participants	62 Participants n=206 Participants	182 Participants n=7 Participants
Region of Enrollment Ukraine	17 Participants n=99 Participants	11 Participants n=107 Participants	12 Participants n=206 Participants	40 Participants n=7 Participants
Region of Enrollment Brazil	44 Participants n=99 Participants	47 Participants n=107 Participants	50 Participants n=206 Participants	141 Participants n=7 Participants
Region of Enrollment Poland	1 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants	5 Participants n=7 Participants
Region of Enrollment Mexico	19 Participants n=99 Participants	19 Participants n=107 Participants	15 Participants n=206 Participants	53 Participants n=7 Participants
Region of Enrollment South Africa	14 Participants n=99 Participants	20 Participants n=107 Participants	17 Participants n=206 Participants	51 Participants n=7 Participants
Region of Enrollment Spain	2 Participants n=99 Participants	4 Participants n=107 Participants	6 Participants n=206 Participants	12 Participants n=7 Participants
Body Weight	88.20 kilogram (kg) STANDARD_DEVIATION 18.488 • n=99 Participants	90.88 kilogram (kg) STANDARD_DEVIATION 18.301 • n=107 Participants	88.14 kilogram (kg) STANDARD_DEVIATION 16.015 • n=206 Participants	89.06 kilogram (kg) STANDARD_DEVIATION 17.653 • n=7 Participants
Body Mass Index (BMI)	32.39 kilogram/square meter (kg/m^2) STANDARD_DEVIATION 5.324 • n=99 Participants	33.00 kilogram/square meter (kg/m^2) STANDARD_DEVIATION 5.546 • n=107 Participants	32.11 kilogram/square meter (kg/m^2) STANDARD_DEVIATION 4.841 • n=206 Participants	32.50 kilogram/square meter (kg/m^2) STANDARD_DEVIATION 5.248 • n=7 Participants
Hemoglobin A1C (HbA1c) at Baseline	8.56 Percentage of HbA1c STANDARD_DEVIATION 0.966 • n=99 Participants	8.57 Percentage of HbA1c STANDARD_DEVIATION 1.088 • n=107 Participants	8.59 Percentage of HbA1c STANDARD_DEVIATION 0.860 • n=206 Participants	8.57 Percentage of HbA1c STANDARD_DEVIATION 0.973 • n=7 Participants
Duration of Diabetes	18.71 years STANDARD_DEVIATION 8.742 • n=99 Participants	17.95 years STANDARD_DEVIATION 8.788 • n=107 Participants	17.57 years STANDARD_DEVIATION 8.722 • n=206 Participants	18.08 years STANDARD_DEVIATION 8.748 • n=7 Participants
Duration of Chronic Kidney Disease (CKD) Stage 3 or Higher	3.47 years STANDARD_DEVIATION 3.998 • n=99 Participants	4.03 years STANDARD_DEVIATION 4.854 • n=107 Participants	4.18 years STANDARD_DEVIATION 5.632 • n=206 Participants	3.89 years STANDARD_DEVIATION 4.872 • n=7 Participants
Estimated Glomerular Filtration Rate (eGFR)	38.5 milliliter/minute/1.73 square meter STANDARD_DEVIATION 12.99 • n=99 Participants	38.3 milliliter/minute/1.73 square meter STANDARD_DEVIATION 12.31 • n=107 Participants	38.1 milliliter/minute/1.73 square meter STANDARD_DEVIATION 13.24 • n=206 Participants	38.3 milliliter/minute/1.73 square meter STANDARD_DEVIATION 12.83 • n=7 Participants

PRIMARY outcome

Timeframe: Baseline, 26 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c data. Only measurements prior to rescue or study drug discontinuation were used.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=175 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=149 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=138 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in Hemoglobin A1c (HbA1c)	-1.13 percentage of HbA1c Standard Error 0.12	-1.12 percentage of HbA1c Standard Error 0.12	-1.19 percentage of HbA1c Standard Error 0.13

SECONDARY outcome

Timeframe: 26 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable post-baseline HbA1c data. Only measurements prior to rescue or study drug discontinuation were used

Percentage of participants whose HbA1c was \<7.0% based on last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Insulin Glargine n=182 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=164 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=152 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Percentage of Participants Whose HbA1c Was <7.0%	34.6 percentage of participants	31.7 percentage of participants	37.5 percentage of participants

SECONDARY outcome

Timeframe: 26 Weeks

Percentage of Participants whose HbA1c was \<8.0% based on last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Insulin Glargine n=182 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=164 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=152 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Percentage of Participants Whose HbA1c Was <8.0%	75.3 percentage of participants	72.6 percentage of participants	78.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c and SMPG data. Only measurements prior to rescue or study drug discontinuation were used.

The daily mean of 8-point SMPG profile at Week 26 is presented. Participants were required to perform two 8-point SMPG profiles over a 1-week period at 5 separate times throughout the study. LS means were calculated using the MMRM model including the corresponding baseline value as a continuous covariate, as well as baseline HbA1c, MA-region, treatment, week, treatment\*week, baseline CKD severity, and log baseline eGFR (within CKD severity).The two 8-point SMPG profiles were collected on two non-consecutive days (pre-meal and 2-hour postprandial SMPG x \[morning, midday, and evening meals in one day\] + bedtime + 5 hours after bedtime).

Outcome measures

Outcome measures
Measure	Insulin Glargine n=128 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=107 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=102 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in 8-Point Self-Monitored Plasma Glucose (SMPG)	-37.6 milligrams/deciliter (mg/dL) Standard Error 3.41	-31.7 milligrams/deciliter (mg/dL) Standard Error 3.53	-33.7 milligrams/deciliter (mg/dL) Standard Error 3.77

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline HbA1c and FG data. Only measurements prior to rescue or study drug discontinuation were used.

LS means were calculated using MMRM with the change in FG as the dependent variable and treatment, MA -region, Baseline CKD Severity, week, treatment\*week, baseline FG, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured

Outcome measures

Outcome measures
Measure	Insulin Glargine n=162 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=145 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=132 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in Fasting Glucose (FG)	-19.1 milligram/deciliter (mg/dL) Standard Deviation 6.00	17.7 milligram/deciliter (mg/dL) Standard Deviation 6.14	23.1 milligram/deciliter (mg/dL) Standard Deviation 6.50

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline HbA1c and insulin lispro dose data. Only measurements prior to rescue or study drug discontinuation were used.

The mean daily insulin was based on a 4-week interval prior to week 26 assessments. LS means were calculated using a REML based mixed-effects model for repeated measures (MMRM) with the change in mean daily insulin as the dependent variable and treatment, MA-region, Baseline HbA1c, baseline mean daily insulin, baseline CKD Severity, week, treatment\*week, log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=177 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=154 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=141 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in Mean Daily Insulin Lispro Dose	16.64 Units/day (U/day) Standard Error 2.76	26.16 Units/day (U/day) Standard Error 2.80	18.12 Units/day (U/day) Standard Error 3.00

SECONDARY outcome

Timeframe: 26 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable HbA1c and average self-monitored plasma glucose post-baseline data. Only measurements prior to rescue or study drug discontinuation were used.

Percentage of Participants With Estimated Average Glucose \<154 milligram/deciliter (mg/dL) was based on last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Insulin Glargine n=134 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=118 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=110 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Percentage of Participants With Estimated Average Glucose <154 mg/dL	64.9 percentage of participants	52.5 percentage of participants	56.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline sCr data.

Change from baseline in serum creatinine (sCr) levels after treatment.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=176 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=169 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=163 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in Serum Creatinine (sCr)	0.10 mg/dL Interval -0.04 to 0.28	0.02 mg/dL Interval -0.15 to 0.15	0.04 mg/dL Interval -0.14 to 0.2

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline eGFR data.

The change in estimated glomerular filtration rate (eGFR) by using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=176 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=169 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=163 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)	-2.5 milliliter/minute/1.73m2 (mL/min/1.73m2) Interval -6.0 to 1.0	-1.0 milliliter/minute/1.73m2 (mL/min/1.73m2) Interval -4.5 to 3.0	-1.0 milliliter/minute/1.73m2 (mL/min/1.73m2) Interval -5.5 to 3.0

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline eCrCl data.

Estimated creatinine clearance (eCrCl) was calculated by Cockcroft-Gault \[Cockcroft and Gault 1976\] equation using baseline estimated lean body weight.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=176 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=169 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=163 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in Estimated Creatinine Clearance (eCrCl)	-2.0 milliliter/minute (ml/min) Interval -4.0 to 0.5	-1.0 milliliter/minute (ml/min) Interval -3.5 to 2.0	-0.5 milliliter/minute (ml/min) Interval -4.0 to 2.0

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline UACR data.

The change from baseline in Urinary Albumin to Creatinine Ratio (UACR).

Outcome measures

Outcome measures
Measure	Insulin Glargine n=181 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=175 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=175 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR)	-1.3 gram/kilogram (g/kg) Interval -71.7 to 62.0	-11.1 gram/kilogram (g/kg) Interval -147.8 to 33.2	-10.2 gram/kilogram (g/kg) Interval -180.5 to 53.1

SECONDARY outcome

Timeframe: Baseline, 26 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline body weight data. Only measurements prior to rescue or study drug discontinuation were used.

LS means were calculated from a REML based MMRM model: Change from Baseline = treatment, week, treatment\*Week, MA-region, Baseline HbA1c (%), Baseline Body Weight (kg), Baseline CKD Severity, Log Baseline eGFR (within CKD severity), where participant enters the model as a random effect. Covariance structure = Unstructured. •

Outcome measures

Outcome measures
Measure	Insulin Glargine n=175 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=151 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=140 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in Body Weight	1.11 kilogram (kg) Standard Error 0.346	-2.02 kilogram (kg) Standard Error 0.357	-2.81 kilogram (kg) Standard Error 0.374

SECONDARY outcome

Timeframe: Baseline through 26 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable post-baseline HE data. Only measurements prior to rescue or study drug discontinuation were used.

Hypoglycemic events (HE) were classified as severe (defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other 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 mmol/L (≤70 mg/dL), nocturnal (defined as any hypoglycemic event that occurs between bedtime and waking). The number of self-reported hypoglycemic events was summarized cumulatively at 26 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=194 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=189 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=190 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Percentage of Participants With Self-Reported Hypoglycemic Events (HE) Total Hypo	71.6 percentage of participants	50.8 percentage of participants	43.2 percentage of participants
Percentage of Participants With Self-Reported Hypoglycemic Events (HE) Documented Symptomatic Hypo	60.3 percentage of participants	40.7 percentage of participants	31.6 percentage of participants
Percentage of Participants With Self-Reported Hypoglycemic Events (HE) Severe Hypo	4.1 percentage of participants	1.1 percentage of participants	0 percentage of participants
Percentage of Participants With Self-Reported Hypoglycemic Events (HE) Nocturnal Hypo	38.1 percentage of participants	15.9 percentage of participants	13.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 26 Weeks

Population: All randomized participants who had received at least one dose of study drug and had evaluable post-baseline HE rate data. Only measurements prior to rescue or study drug discontinuation were used.

Hypoglycemic events (HE) were classified as total HE rate, documented symptomatic hypoglycemia, severe hypoglycemia, and nocturnal. The 1-year adjusted rate of HEs was summarized cumulatively at 26 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=194 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=189 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=190 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Rate of Hypoglycemic Events Total HE Rate	17.07 Events/Participant/Year Standard Deviation 27.70	7.76 Events/Participant/Year Standard Deviation 20.39	5.45 Events/Participant/Year Standard Deviation 12.54
Rate of Hypoglycemic Events Documented Symptomatic HE Rate	11.34 Events/Participant/Year Standard Deviation 22.04	4.86 Events/Participant/Year Standard Deviation 13.37	4.19 Events/Participant/Year Standard Deviation 11.58
Rate of Hypoglycemic Events Severe HE Rate	0.10 Events/Participant/Year Standard Deviation 0.56	0.03 Events/Participant/Year Standard Deviation 0.31	0.00 Events/Participant/Year Standard Deviation 0.00
Rate of Hypoglycemic Events Nocturnal HE Rate	3.06 Events/Participant/Year Standard Deviation 7.26	0.73 Events/Participant/Year Standard Deviation 2.25	0.63 Events/Participant/Year Standard Deviation 2.26

SECONDARY outcome

Timeframe: Baseline, 52 Weeks

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS means in HbA1c were calculated using a REML based mixed-effects model for repeated measures (MMRM) with the change in HbA1c as the dependent variable and treatment, MA region, Baseline CKD Severity, week, treatment\*week, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=153 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=132 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=130 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in HbA1c	-1.00 percentage of HbA1c Standard Error 0.12	-1.10 percentage of HbA1c Standard Error 0.12	-1.10 percentage of HbA1c Standard Error 0.13

SECONDARY outcome

Timeframe: 52 Weeks

Percentage of participants whose HbA1c was \<7.0% based on last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Insulin Glargine n=182 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=164 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=152 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Percentage of Participants Whose HbA1c is <7.0%	29.1 percentage of participants	33.5 percentage of participants	32.9 percentage of participants

SECONDARY outcome

Timeframe: 52 Weeks

Percentage of participants whose HbA1c was \<8.0% based on last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Insulin Glargine n=182 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=164 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=152 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Percentage of Participants Whose HbA1c is <8.0%	70.3 percentage of participants	69.5 percentage of participants	69.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 52 Weeks

The daily mean of 8-point SMPG profile at Week 52 is presented. Participants were required to perform two 8-point SMPG profiles over a 1-week period at 5 separate times throughout the study. LS means were calculated using the MMRM model including the corresponding baseline value as a continuous covariate, as well as baseline HbA1c, MA-region, treatment, week, treatment\*week, baseline CKD severity, and log baseline eGFR (within CKD severity).The two 8-point SMPG profiles were collected on two non-consecutive days (pre-meal and 2-hour postprandial SMPG x \[morning, midday, and evening meals in one day\] + bedtime + 5 hours after bedtime).

Outcome measures

Outcome measures
Measure	Insulin Glargine n=118 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=96 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=102 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in 8-Point SMPG	-40.5 mg/dL Standard Error 3.59	-30.0 mg/dL Standard Error 3.75	-27.2 mg/dL Standard Error 3.93

SECONDARY outcome

Timeframe: Baseline, 52 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c and FG data. Only measurements prior to rescue or study drug discontinuation were used.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=152 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=132 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=131 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in FG	-6.4 mg/dL Standard Error 6.38	20.8 mg/dL Standard Error 6.58	28.3 mg/dL Standard Error 6.87

SECONDARY outcome

Timeframe: Baseline, 52 Weeks

The mean daily insulin was based on a 4-week interval prior to week 52 assessments. LS means were calculated using a REML based mixed-effects model for repeated measures (MMRM) with the change in mean daily insulin as the dependent variable and treatment, MA-region, Baseline HbA1c, baseline mean daily insulin, baseline CKD Severity, week, treatment\*week, log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=159 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=140 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=132 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change in Mean Daily Insulin Lispro Dose	16.84 U/day Standard Error 2.87	27.46 U/day Standard Error 2.93	20.05 U/day Standard Error 3.13

SECONDARY outcome

Timeframe: 52 Weeks

Percentage of Participants With Estimated Average Glucose \<154 milligram/deciliter (mg/dL) was based on last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Insulin Glargine n=137 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=122 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=116 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Percentage of Participants With Estimated Average Glucose <154 mg/dL	73.7 percentage of participants	57.4 percentage of participants	50.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 52 Weeks

Population: All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline sCr data.

Change from baseline in sCr levels after treatment.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=164 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=160 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=157 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in sCr	0.12 mg/dL Interval -0.05 to 0.38	0.04 mg/dL Interval -0.11 to 0.27	0.07 mg/dL Interval -0.11 to 0.21

SECONDARY outcome

Timeframe: Baseline, 52 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline eGFR data.

The change in eGFR by using CKD-EPI equation.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=164 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=160 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=157 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in eGFR	-3.3 mL/min/1.73m2 Interval -7.5 to 1.0	-1.5 mL/min/1.73m2 Interval -5.5 to 2.5	-2.0 mL/min/1.73m2 Interval -6.0 to 2.5

SECONDARY outcome

Timeframe: Baseline, 52 Weeks

Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline eCrCl data.

eCrCl was calculated by Cockcroft-Gault \[Cockcroft and Gault 1976\] equation using baseline estimated lean body weight.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=164 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=160 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=157 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in eCrCl	-2.5 mL/min Interval -5.8 to 0.5	-1.3 mL/min Interval -4.0 to 1.5	-1.5 mL/min Interval -5.0 to 1.5

SECONDARY outcome

Timeframe: Baseline, 52 Weeks

Population: All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline UACR data.

The change from baseline in UACR

Outcome measures

Outcome measures
Measure	Insulin Glargine n=165 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=162 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=159 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in UACR	3.5 g/kg Interval -56.2 to 138.1	-3.0 g/kg Interval -88.5 to 87.6	-11.5 g/kg Interval -158.0 to 42.9

SECONDARY outcome

Timeframe: Baseline, 52 Weeks

LS means were calculated from a REML based MMRM model: Change from Baseline = treatment , week, treatment\*Week, MA-region, Baseline HbA1c (%), Baseline Body Weight (kg), Baseline CKD Severity, Log Baseline eGFR (within CKD severity), where participant enters the model as a random effect. Covariance structure = Unstructured.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=158 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=137 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=132 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Change From Baseline in Body Weight	1.57 kg Standard Error 0.429	-1.71 kg Standard Error 0.448	-2.66 kg Standard Error 0.467

SECONDARY outcome

Timeframe: Baseline through 52 Weeks

Hypoglycemic events (HE) were classified as severe (defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other 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 mmol/L (≤70 mg/dL), nocturnal (defined as any hypoglycemic event that occurs between bedtime and waking). The number of self-reported hypoglycemic events was summarized cumulatively at 52 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=194 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=189 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=190 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Percentage of Participants With Self-Reported Hypoglycemic Events (HE) Total Hypo	74.7 percentage of participants	59.8 percentage of participants	50.0 percentage of participants
Percentage of Participants With Self-Reported Hypoglycemic Events (HE) Documented Symptomatic Hypo	63.4 percentage of participants	48.1 percentage of participants	40.5 percentage of participants
Percentage of Participants With Self-Reported Hypoglycemic Events (HE) Severe Hypo	6.7 percentage of participants	2.6 percentage of participants	0 percentage of participants
Percentage of Participants With Self-Reported Hypoglycemic Events (HE) Nocturnal Hypo	47.9 percentage of participants	23.8 percentage of participants	20.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 52 Weeks

HE were classified as total HE rate, documented symptomatic hypoglycemia, severe hypoglycemia, and nocturnal. The 1-year adjusted rate of HEs was summarized cumulatively at 52 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=194 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=189 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=190 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Rate of Hypoglycemic Events (HE) Total HE Rate	14.36 Events/Participant/Year Standard Deviation 22.20	7.59 Events/Participant/Year Standard Deviation 17.81	5.82 Events/Participant/Year Standard Deviation 13.70
Rate of Hypoglycemic Events (HE) Documented Symptomatic HE Rate	9.62 Events/Participant/Year Standard Deviation 17.72	4.34 Events/Participant/Year Standard Deviation 9.30	4.44 Events/Participant/Year Standard Deviation 12.23
Rate of Hypoglycemic Events (HE) Severe HE Rate	0.09 Events/Participant/Year Standard Deviation 0.37	0.03 Events/Participant/Year Standard Deviation 0.21	0.00 Events/Participant/Year Standard Deviation 0.00
Rate of Hypoglycemic Events (HE) Nocturnal HE Rate	2.48 Events/Participant/Year Standard Deviation 5.10	0.76 Events/Participant/Year Standard Deviation 2.09	0.70 Events/Participant/Year Standard Deviation 2.29

SECONDARY outcome

Timeframe: Baseline through 52 Weeks

Population: All randomized participants who received at least one dose of study drug.

Participants with Events of Allergic/Hypersensitivity Reactions: Angioedema Standardized MedDRA Query (SMQ), Anaphylactic Reaction SMQ, or Severe Cutaneous Adverse Reactions SMQ

Outcome measures

Outcome measures
Measure	Insulin Glargine n=194 Participants Insulin glargine was administered subcutaneous (SC) at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=190 Participants Dulaglutide 0.75 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=192 Participants Dulaglutide 1.5 mg was administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Participants With Events of Allergic/Hypersensitivity Reactions Angioedema SMQ	1 participants with events	2 participants with events	2 participants with events
Participants With Events of Allergic/Hypersensitivity Reactions Angioedema	0 participants with events	0 participants with events	1 participants with events
Participants With Events of Allergic/Hypersensitivity Reactions Eyelid edema	0 participants with events	1 participants with events	0 participants with events
Participants With Events of Allergic/Hypersensitivity Reactions Face edema	0 participants with events	1 participants with events	1 participants with events
Participants With Events of Allergic/Hypersensitivity Reactions Urticaria	1 participants with events	0 participants with events	0 participants with events
Participants With Events of Allergic/Hypersensitivity Reactions Anaphylactic Reaction SMQ	1 participants with events	0 participants with events	0 participants with events
Participants With Events of Allergic/Hypersensitivity Reactions Circulatory collapse	1 participants with events	0 participants with events	0 participants with events
Participants With Events of Allergic/Hypersensitivity Reactions Severe Cutaneous Adverse Reactions SMQ	0 participants with events	0 participants with events	0 participants with events

Adverse Events

Insulin Glargine

Serious events: 56 serious events

Other events: 130 other events

Deaths: 0 deaths

Dulaglutide 0.75 mg

Serious events: 48 serious events

Other events: 134 other events

Deaths: 0 deaths

Dulaglutide 1.5 mg

Serious events: 41 serious events

Other events: 144 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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

Measure	Insulin Glargine n=194 participants at risk Insulin glargine administered SC to be given at bedtime per sliding scale. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 0.75 mg n=190 participants at risk Dulaglutide 0.75 mg administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.	Dulaglutide 1.5 mg n=192 participants at risk Dulaglutide 1.5 mg administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day.
Blood and lymphatic system disorders Anaemia	5.2% 10/194 • Number of events 10 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	1.6% 3/190 • Number of events 3 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	2.6% 5/192 • Number of events 5 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	3.1% 6/194 • Number of events 6 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	5.3% 10/190 • Number of events 10 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	6.2% 12/192 • Number of events 13 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	7.2% 14/194 • Number of events 17 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	15.8% 30/190 • Number of events 37 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	16.1% 31/192 • Number of events 49 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	4.6% 9/194 • Number of events 9 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	14.2% 27/190 • Number of events 38 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	19.8% 38/192 • Number of events 52 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	4.6% 9/194 • Number of events 9 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	8.4% 16/190 • Number of events 22 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	13.5% 26/192 • Number of events 42 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
General disorders Oedema peripheral	7.7% 15/194 • Number of events 16 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	6.3% 12/190 • Number of events 13 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	5.2% 10/192 • Number of events 10 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Infections and infestations Influenza	5.2% 10/194 • Number of events 10 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	7.9% 15/190 • Number of events 18 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	6.2% 12/192 • Number of events 12 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	6.2% 12/194 • Number of events 15 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	4.7% 9/190 • Number of events 12 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	5.7% 11/192 • Number of events 12 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Infections and infestations Sinusitis	5.7% 11/194 • Number of events 13 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	2.1% 4/190 • Number of events 4 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	1.0% 2/192 • Number of events 2 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	10.3% 20/194 • Number of events 26 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	6.8% 13/190 • Number of events 15 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	4.2% 8/192 • Number of events 9 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	9.8% 19/194 • Number of events 25 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	5.3% 10/190 • Number of events 12 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	6.8% 13/192 • Number of events 16 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Investigations Blood creatinine increased	46.4% 90/194 • Number of events 124 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	37.4% 71/190 • Number of events 102 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	38.5% 74/192 • Number of events 106 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Investigations Glomerular filtration rate decreased	13.4% 26/194 • Number of events 29 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	10.5% 20/190 • Number of events 25 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	8.9% 17/192 • Number of events 22 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Investigations Weight increased	8.2% 16/194 • Number of events 18 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	4.7% 9/190 • Number of events 9 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	4.7% 9/192 • Number of events 10 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	1.5% 3/194 • Number of events 3 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	2.6% 5/190 • Number of events 6 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	5.7% 11/192 • Number of events 11 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	6.7% 13/194 • Number of events 15 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	4.2% 8/190 • Number of events 10 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	6.2% 12/192 • Number of events 14 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	3.6% 7/194 • Number of events 8 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	4.2% 8/190 • Number of events 8 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	5.2% 10/192 • Number of events 10 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Nervous system disorders Dizziness	5.2% 10/194 • Number of events 12 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	5.8% 11/190 • Number of events 12 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	4.2% 8/192 • Number of events 11 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 15/194 • Number of events 17 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	3.7% 7/190 • Number of events 7 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	3.6% 7/192 • Number of events 8 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.
Vascular disorders Hypertension	10.3% 20/194 • Number of events 20 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	6.8% 13/190 • Number of events 13 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.	7.3% 14/192 • Number of events 14 • Up To Week 52 Safety population included those participants who received at least one dose of study drug.