Trial Outcomes & Findings for A Study of Dulaglutide (LY2189265) in Participants With Type II Diabetes (NCT NCT02152371)

NCT ID: NCT02152371

Last Updated: 2019-09-25

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-squares (LS) mean and standard error (SE) changes from baseline in HbA1c at 28 weeks were measured using mixed model regression and restricted maximum likelihood (REML) with treatment, pooled country, visit, and treatment-by -visit interaction as fixed effects, baseline as covariate, and participant as a random effect.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

300 participants

Primary outcome timeframe

Baseline, 28 Weeks

Results posted on

2019-09-25

Participant Flow

All eligible participants entered a 2-week lead-in period. Only those participants who required further up-titration of the insulin glargine dose per treat-to-target (TTT) algorithm were randomized to one of two treatment groups.

Participant milestones

Participant milestones
Measure
Dulaglutide + Insulin Glargine
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Placebo + Insulin Glargine
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Overall Study
STARTED
150
150
Overall Study
Received at Least 1 Dose of Study Drug.
150
150
Overall Study
COMPLETED
138
134
Overall Study
NOT COMPLETED
12
16

Reasons for withdrawal

Reasons for withdrawal
Measure
Dulaglutide + Insulin Glargine
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Placebo + Insulin Glargine
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Overall Study
Adverse Event
6
2
Overall Study
Withdrawal by Subject
3
7
Overall Study
Protocol Violation
2
3
Overall Study
Lost to Follow-up
1
0
Overall Study
Lack of Efficacy
0
1
Overall Study
Physician Decision
0
2
Overall Study
Reason Not Given
0
1

Baseline Characteristics

A Study of Dulaglutide (LY2189265) in Participants With Type II Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Total
n=300 Participants
Total of all reporting groups
Age, Continuous
60.2 years
STANDARD_DEVIATION 9.47 • n=5 Participants
60.6 years
STANDARD_DEVIATION 10.07 • n=7 Participants
60.4 years
STANDARD_DEVIATION 9.76 • n=5 Participants
Sex: Female, Male
Female
65 Participants
n=5 Participants
62 Participants
n=7 Participants
127 Participants
n=5 Participants
Sex: Female, Male
Male
85 Participants
n=5 Participants
88 Participants
n=7 Participants
173 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
26 Participants
n=5 Participants
25 Participants
n=7 Participants
51 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
104 Participants
n=5 Participants
104 Participants
n=7 Participants
208 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
20 Participants
n=5 Participants
21 Participants
n=7 Participants
41 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
1 Participants
n=5 Participants
2 Participants
n=7 Participants
3 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
5 Participants
n=5 Participants
6 Participants
n=7 Participants
11 Participants
n=5 Participants
Race (NIH/OMB)
White
143 Participants
n=5 Participants
138 Participants
n=7 Participants
281 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
Czech Republic
25 participants
n=5 Participants
27 participants
n=7 Participants
52 participants
n=5 Participants
Region of Enrollment
Puerto Rico
12 participants
n=5 Participants
16 participants
n=7 Participants
28 participants
n=5 Participants
Region of Enrollment
Hungary
37 participants
n=5 Participants
35 participants
n=7 Participants
72 participants
n=5 Participants
Region of Enrollment
United States
32 participants
n=5 Participants
29 participants
n=7 Participants
61 participants
n=5 Participants
Region of Enrollment
Italy
13 participants
n=5 Participants
15 participants
n=7 Participants
28 participants
n=5 Participants
Region of Enrollment
United Kingdom
2 participants
n=5 Participants
2 participants
n=7 Participants
4 participants
n=5 Participants
Region of Enrollment
Spain
29 participants
n=5 Participants
26 participants
n=7 Participants
55 participants
n=5 Participants
Mean Insulin Glargine Dose
40.71 Units (U)
STANDARD_DEVIATION 23.12 • n=5 Participants
36.59 Units (U)
STANDARD_DEVIATION 21.46 • n=7 Participants
38.65 Units (U)
STANDARD_DEVIATION 22.37 • n=5 Participants
Metformin Use at Baseline
Treated with Metformin
134 participants
n=5 Participants
131 participants
n=7 Participants
265 participants
n=5 Participants
Metformin Use at Baseline
Not Treated with Metformin
16 participants
n=5 Participants
19 participants
n=7 Participants
35 participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 28 Weeks

Population: All participants who received at least one dose of study drug and had evaluable baseline and post- baseline HbA1c.

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least-squares (LS) mean and standard error (SE) changes from baseline in HbA1c at 28 weeks were measured using mixed model regression and restricted maximum likelihood (REML) with treatment, pooled country, visit, and treatment-by -visit interaction as fixed effects, baseline as covariate, and participant as a random effect.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Change From Baseline to 28 Weeks in Hemoglobin A1c (HbA1c)
-1.44 percentage of change
Standard Error 0.09
-0.67 percentage of change
Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, 28 Weeks

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

FSG is a test to determine glucose levels after an overnight fast. LS means FSG change from baseline to primary endpoint at week 28 was calculated using a mixed effects model for repeated measures (MMRM) analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline FSG as covariate.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Change From Baseline to 28 Weeks in Fasting Serum Glucose (FSG)
-44.63 milligram per deciliter (mg/dL)
Standard Error 4.16
-27.90 milligram per deciliter (mg/dL)
Standard Error 4.08

SECONDARY outcome

Timeframe: Baseline, 28 Weeks

Population: All randomized participants who received at least 1 dose of study drug and had evaluable baseline and post-baseline SMPG data.

The LS means of the 7-point SMPG change from baseline to primary endpoint at week 28 was measured using a MMRM analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline SMPG as covariate.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)
Pre-Morning Meal (n=133,129)
-44.03 mg/dL
Standard Error 2.71
-35.97 mg/dL
Standard Error 2.64
Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)
Morning Meal 2-Hour Postprandial (n=123,119)
-64.16 mg/dL
Standard Error 4.31
-46.97 mg/dL
Standard Error 4.27
Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)
Pre-Midday Meal (n=133,127)
-40.89 mg/dL
Standard Error 3.72
-25.34 mg/dL
Standard Error 3.62
Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)
Midday Meal 2-Hour Post Prandial (n=123,117)
-51.13 mg/dL
Standard Error 4.40
-32.98 mg/dL
Standard Error 4.33
Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)
Pre-Evening Meal (n=133,129)
-43.68 mg/dL
Standard Error 4.21
-28.71 mg/dL
Standard Error 4.07
Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)
Evening Meal 2-Hour Postprandial (n=126,122)
-48.63 mg/dL
Standard Error 5.22
-27.35 mg/dL
Standard Error 5.16
Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)
3:00 AM (Morning) (n=124,117)
-39.77 mg/dL
Standard Error 4.27
-20.30 mg/dL
Standard Error 4.23

SECONDARY outcome

Timeframe: Baseline, 28 Weeks

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

LS means of the body weight change from baseline to primary endpoint at week 28 was adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline body weight as covariate, via a MMRM analysis.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Change From Baseline to 28 Weeks in Body Weight
-1.91 kilogram(kg)
Standard Error 0.30
0.50 kilogram(kg)
Standard Error 0.30

SECONDARY outcome

Timeframe: Baseline, 28 Weeks

Population: All participants who one dose of study drug and had evaluable baseline and post-baseline insulin glargine data.

Least Square (LS) Means of the insulin dose change from baseline to primary endpoint at week 28 was adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline insulin dose as covariate, via a MMRM analysis.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Change From Baseline to 28 Weeks in Daily Mean Insulin Glargine Dose
12.75 units (u)
Standard Error 2.27
25.94 units (u)
Standard Error 2.30

SECONDARY outcome

Timeframe: Baseline through 28 Weeks

Population: All randomized participants who received at least 1 dose of study.

Cardiovascular (CV) adverse events (AEs) were adjudicated by an independent committee of physicians with cardiology expertise external to the sponsor. Deaths occurring during the study treatment period and nonfatal CV AEs were to be adjudicated. Nonfatal CV events that were to be adjudicated were myocardial infarction; hospitalization for unstable angina; hospitalization for heart failure; coronary interventions (such as coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI); and cerebrovascular events, including cerebrovascular accident (CVA/stroke), and transient ischemic attack (TIA).

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Number of Participants With Investigator Reported and Adjudicated Cardiovascular Events
3 participants
1 participants

SECONDARY outcome

Timeframe: Baseline through 28 Weeks

Population: All randomized participants who received at least 1 dose of study drug.

Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =\<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =\<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The percentage of participants with self-reported hypoglycemic events is presented.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Percentage of Participants With Self-Reported Events of Hypoglycemia
Symptomatic
35.3 percentage of participants
30.0 percentage of participants
Percentage of Participants With Self-Reported Events of Hypoglycemia
Asymptomatic
42.7 percentage of participants
39.3 percentage of participants
Percentage of Participants With Self-Reported Events of Hypoglycemia
Severe
0.7 percentage of participants
0.0 percentage of participants
Percentage of Participants With Self-Reported Events of Hypoglycemia
Nocturnal
28.0 percentage of participants
28.7 percentage of participants
Percentage of Participants With Self-Reported Events of Hypoglycemia
Probable Symptomatic
2.7 percentage of participants
2.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 28 Weeks

Population: All randomized participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Percentage of Participants Discontinuing the Study Due to Severe, Persistent Hyperglycemia
0 percentage of participants
0 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 28 Weeks

Population: All randomized participants who received at least 1 dose of study drug.

The number of cases of acute pancreatitis confirmed by adjudication. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Number of Participants With Adjudicated Acute Pancreatitis Events
0 participants
0 participants

SECONDARY outcome

Timeframe: Baseline through 28 Weeks

Population: All randomized participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Number of Participants With Thyroid Tumors/Neoplasms (Including C-Cell Hyperplasia)
1 participants
0 participants

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 28

Population: All randomized participants who received at least 1 dose of study drug and had at least one post-baseline Dulaglutide ADA test result.

Dulaglutide anti-drug antibodies (ADA) were assessed at baseline, Weeks 12 and 28. A participant was considered to have treatment-emergent (TE) dulaglutide ADAs if the participant had at least 1 titer that was TE relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=149 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=149 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Number of Participants With Dulaglutide Anti-Drug Antibodies
0 participants
2 participants

SECONDARY outcome

Timeframe: 28 Weeks

Population: All randomized participants who received at least 1 dose of study drug and had a baseline and post-baseline HbA1c data. Last observation carried forward (LOCF) methodology was used to impute missing post-baseline values.

Percentage of participants who achieved HbA1c levels of \<7% or ≤6.5% were analyzed using a logistic regression model, controlling for treatment, pre-treatment, baseline HbA1c and country.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Percentage of Participants Achieving HbA1c Targets of <7.0% or ≤6.5%
HbA1c <= 6.5
50.7 percentage of participants
16.7 percentage of participants
Percentage of Participants Achieving HbA1c Targets of <7.0% or ≤6.5%
HbA1c < 7.0
69.3 percentage of participants
35.3 percentage of participants

SECONDARY outcome

Timeframe: 28 Weeks

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline HbA1c data.Last observation carried forward (LOCF) methodology was used to impute missing post-baseline values.

Percentage of participants who achieved a target HbA1c target of \<7%, without weight gain and without documented symptomatic hypoglycemia at 28 weeks were analyzed using regression model, controlling for treatment, pre-treatment, baseline HbA1c and country.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 Kilograms [kg]) at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)
40.7 percentage of participants
16.7 percentage of participants

SECONDARY outcome

Timeframe: 28 Weeks

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline HbA1c data. Last observation carried forward (LOCF) methodology was used to impute missing post-baseline values

Percentage of participants achieving target HbA1c of \<7.0% at 28 weeks without documented symptomatic hypoglycemia are presented. Documented symptomatic hypoglycemia is defined as any time a participant experienced symptoms and or signs associated with hypoglycemia and had a plasma glucose of \<=70 mg/dL.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Percentage of Participants Achieving HbA1c Target of <7.0% at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)
52.0 percentage of participants
28.0 percentage of participants

SECONDARY outcome

Timeframe: 28 Weeks

Population: All randomized participants who received at least 1 dose of study drug and had baseline and post-baseline HbA1c data. Last observation carried forward (LOCF) methodology was used to impute missing post-baseline values.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 kg)
52.7 percentage of participants
20.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 28 Weeks

Population: All randomized participants who received at least 1 dose of study drug.

The rate of total hypoglycemic events any type per 30 days is presented. The hypoglycemia rate per 30 days during defined period is calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period\*30 days.

Outcome measures

Outcome measures
Measure
Dulaglutide + Insulin Glargine
n=150 Participants
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 Participants
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Rate of Hypoglycemic Events up to 28 Weeks
0.63 rate of hypoglycemic events per 30 days
Standard Deviation 1.24
0.70 rate of hypoglycemic events per 30 days
Standard Deviation 1.32

Adverse Events

Dulaglutide + Insulin Glargine

Serious events: 9 serious events
Other events: 51 other events
Deaths: 0 deaths

Placebo + Insulin Glargine

Serious events: 7 serious events
Other events: 29 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Dulaglutide + Insulin Glargine
n=150 participants at risk
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 participants at risk
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Cardiac disorders
Angina unstable
0.67%
1/150 • Number of events 1
0.67%
1/150 • Number of events 1
Cardiac disorders
Atrial fibrillation
0.67%
1/150 • Number of events 1
0.00%
0/150
Cardiac disorders
Bradycardia
1.3%
2/150 • Number of events 2
0.00%
0/150
Cardiac disorders
Coronary artery disease
0.67%
1/150 • Number of events 1
0.00%
0/150
Cardiac disorders
Myocardial infarction
0.67%
1/150 • Number of events 1
0.00%
0/150
General disorders
Non-cardiac chest pain
0.00%
0/150
0.67%
1/150 • Number of events 1
Hepatobiliary disorders
Granulomatous liver disease
0.67%
1/150 • Number of events 1
0.00%
0/150
Infections and infestations
Gastroenteritis
0.67%
1/150 • Number of events 1
0.00%
0/150
Infections and infestations
Viral infection
0.00%
0/150
0.67%
1/150 • Number of events 1
Injury, poisoning and procedural complications
Lower limb fracture
0.67%
1/150 • Number of events 1
0.00%
0/150
Metabolism and nutrition disorders
Hypoglycaemia
0.67%
1/150 • Number of events 1
0.00%
0/150
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
0.00%
0/150
0.67%
1/150 • Number of events 1
Musculoskeletal and connective tissue disorders
Osteoarthritis
0.00%
0/150
0.67%
1/150 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer
0.00%
0/150
0.67%
1/150 • Number of events 1
Nervous system disorders
Carotid artery stenosis
0.67%
1/150 • Number of events 1
0.00%
0/150
Nervous system disorders
Cerebral infarction
0.67%
1/150 • Number of events 1
0.00%
0/150
Nervous system disorders
Transient ischaemic attack
1.3%
2/150 • Number of events 2
0.00%
0/150
Skin and subcutaneous tissue disorders
Skin ulcer
0.00%
0/150
0.67%
1/150 • Number of events 1

Other adverse events

Other adverse events
Measure
Dulaglutide + Insulin Glargine
n=150 participants at risk
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Dulaglutide: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Placebo + Insulin Glargine
n=150 participants at risk
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses. Placebo: Administered SQ Insulin Glargine: Administered SQ Metformin: Administered orally
Gastrointestinal disorders
Diarrhoea
11.3%
17/150 • Number of events 19
4.0%
6/150 • Number of events 6
Gastrointestinal disorders
Dyspepsia
6.0%
9/150 • Number of events 9
0.00%
0/150
Gastrointestinal disorders
Nausea
12.0%
18/150 • Number of events 23
1.3%
2/150 • Number of events 3
Gastrointestinal disorders
Vomiting
6.0%
9/150 • Number of events 11
0.00%
0/150
Infections and infestations
Nasopharyngitis
4.0%
6/150 • Number of events 7
9.3%
14/150 • Number of events 19
Infections and infestations
Upper respiratory tract infection
7.3%
11/150 • Number of events 18
6.7%
10/150 • Number of events 10
Metabolism and nutrition disorders
Decreased appetite
6.7%
10/150 • Number of events 11
0.00%
0/150

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 1-800-545-5979

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60