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Trial record 26 of 39 for:    LY2189265

A Study of Dulaglutide (LY2189265) in Participants With Type II Diabetes (AWARD-9)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02152371
Recruitment Status : Completed
First Posted : June 2, 2014
Results First Posted : December 7, 2016
Last Update Posted : December 7, 2016
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Dulaglutide
Drug: Placebo
Drug: Insulin Glargine
Drug: Metformin
Enrollment 300

Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description 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 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.
Period Title: Overall Study
Started 150 150
Received at Least 1 Dose of Study Drug. 150 150
Completed 138 134
Not Completed 12 16
Reason Not Completed
Adverse Event             6             2
Withdrawal by Subject             3             7
Protocol Violation             2             3
Lost to Follow-up             1             0
Lack of Efficacy             0             1
Physician Decision             0             2
Reason Not Given             0             1
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine Total
Hide Arm/Group Description 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 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 of all reporting groups
Overall Number of Baseline Participants 150 150 300
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 150 participants 150 participants 300 participants
60.2  (9.47) 60.6  (10.07) 60.4  (9.76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 150 participants 150 participants 300 participants
Female
65
  43.3%
62
  41.3%
127
  42.3%
Male
85
  56.7%
88
  58.7%
173
  57.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 150 participants 150 participants 300 participants
Hispanic or Latino
26
  17.3%
25
  16.7%
51
  17.0%
Not Hispanic or Latino
104
  69.3%
104
  69.3%
208
  69.3%
Unknown or Not Reported
20
  13.3%
21
  14.0%
41
  13.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 150 participants 150 participants 300 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   0.7%
1
   0.3%
Native Hawaiian or Other Pacific Islander
1
   0.7%
2
   1.3%
3
   1.0%
Black or African American
5
   3.3%
6
   4.0%
11
   3.7%
White
143
  95.3%
138
  92.0%
281
  93.7%
More than one race
1
   0.7%
3
   2.0%
4
   1.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 150 participants 150 participants 300 participants
Czech Republic 25 27 52
Puerto Rico 12 16 28
Hungary 37 35 72
United States 32 29 61
Italy 13 15 28
United Kingdom 2 2 4
Spain 29 26 55
Mean Insulin Glargine Dose  
Mean (Standard Deviation)
Unit of measure:  Units (U)
Number Analyzed 150 participants 150 participants 300 participants
40.71  (23.12) 36.59  (21.46) 38.65  (22.37)
Metformin Use at Baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 150 participants 150 participants 300 participants
Treated with Metformin 134 131 265
Not Treated with Metformin 16 19 35
1.Primary Outcome
Title Change From Baseline to 28 Weeks in Hemoglobin A1c (HbA1c)
Hide Description 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.
Time Frame Baseline, 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug and had evaluable baseline and post- baseline HbA1c.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Least Squares Mean (Standard Error)
Unit of Measure: percentage of change
-1.44  (0.09) -0.67  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means Diff
Estimated Value -0.77
Confidence Interval (2-Sided) 95%
-0.97 to -0.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to 28 Weeks in Fasting Serum Glucose (FSG)
Hide Description 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.
Time Frame Baseline, 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug and had evaluable baseline and post-baseline FSG data.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Least Squares Mean (Standard Error)
Unit of Measure: milligram per deciliter (mg/dL)
-44.63  (4.16) -27.90  (4.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff
Estimated Value -16.73
Confidence Interval (2-Sided) 95%
-26.02 to -7.44
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.72
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)
Hide Description 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.
Time Frame Baseline, 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had evaluable baseline and post-baseline SMPG data.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Pre-Morning Meal (n=133,129) -44.03  (2.71) -35.97  (2.64)
Morning Meal 2-Hour Postprandial (n=123,119) -64.16  (4.31) -46.97  (4.27)
Pre-Midday Meal (n=133,127) -40.89  (3.72) -25.34  (3.62)
Midday Meal 2-Hour Post Prandial (n=123,117) -51.13  (4.40) -32.98  (4.33)
Pre-Evening Meal (n=133,129) -43.68  (4.21) -28.71  (4.07)
Evening Meal 2-Hour Postprandial (n=126,122) -48.63  (5.22) -27.35  (5.16)
3:00 AM (Morning) (n=124,117) -39.77  (4.27) -20.30  (4.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments Pre-Morning Meal
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .007
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff
Estimated Value -8.06
Confidence Interval (2-Sided) 95%
-13.87 to -2.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.95
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments Morning Meal 2-Hour Postprandial
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff
Estimated Value -17.18
Confidence Interval (2-Sided) 95%
-25.96 to -8.40
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.45
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments Pre-Midday Meal
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff
Estimated Value -15.55
Confidence Interval (2-Sided) 95%
-23.58 to -7.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.08
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments Midday Meal 2-Hour Postprandial
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff
Estimated Value -18.15
Confidence Interval (2-Sided) 95%
-27.18 to -9.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.58
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments Pre-Evening Meal
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff
Estimated Value -14.96
Confidence Interval (2-Sided) 95%
-23.93 to -5.99
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.55
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments Evening Meal 2-Hour Postprandial
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff
Estimated Value -21.28
Confidence Interval (2-Sided) 95%
-32.46 to -10.10
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.68
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments 3:00AM (Morning)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff
Estimated Value -19.48
Confidence Interval (2-Sided) 95%
-28.77 to -10.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.72
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to 28 Weeks in Body Weight
Hide Description 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.
Time Frame Baseline, 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug and had evaluable baseline and post-baseline body weight data.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Least Squares Mean (Standard Error)
Unit of Measure: kilogram(kg)
-1.91  (0.30) 0.50  (0.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means Difference
Estimated Value -2.41
Confidence Interval (2-Sided) 95%
-3.19 to -1.64
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.39
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline to 28 Weeks in Daily Mean Insulin Glargine Dose
Hide Description 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.
Time Frame Baseline, 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who one dose of study drug and had evaluable baseline and post-baseline insulin glargine data.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Least Squares Mean (Standard Error)
Unit of Measure: units (u)
12.75  (2.27) 25.94  (2.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Means Diff
Estimated Value -13.19
Confidence Interval (2-Sided) 95%
-19.55 to -6.84
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.21
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With Investigator Reported and Adjudicated Cardiovascular Events
Hide Description 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).
Time Frame Baseline through 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Measure Type: Number
Unit of Measure: participants
3 1
7.Secondary Outcome
Title Percentage of Participants With Self-Reported Events of Hypoglycemia
Hide Description 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.
Time Frame Baseline through 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Measure Type: Number
Unit of Measure: percentage of participants
Symptomatic 35.3 30.0
Asymptomatic 42.7 39.3
Severe 0.7 0.0
Nocturnal 28.0 28.7
Probable Symptomatic 2.7 2.0
8.Secondary Outcome
Title Percentage of Participants Discontinuing the Study Due to Severe, Persistent Hyperglycemia
Hide Description [Not Specified]
Time Frame Baseline through 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Measure Type: Number
Unit of Measure: percentage of participants
0 0
9.Secondary Outcome
Title Number of Participants With Adjudicated Acute Pancreatitis Events
Hide Description 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.
Time Frame Baseline through 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Measure Type: Number
Unit of Measure: participants
0 0
10.Secondary Outcome
Title Number of Participants With Thyroid Tumors/Neoplasms (Including C-Cell Hyperplasia)
Hide Description [Not Specified]
Time Frame Baseline through 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Measure Type: Number
Unit of Measure: participants
1 0
11.Secondary Outcome
Title Number of Participants With Dulaglutide Anti-Drug Antibodies
Hide Description 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.
Time Frame Baseline, Week 12 and Week 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had at least one post-baseline Dulaglutide ADA test result.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 149 149
Measure Type: Number
Unit of Measure: participants
0 2
12.Secondary Outcome
Title Percentage of Participants Achieving HbA1c Targets of <7.0% or ≤6.5%
Hide Description 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.
Time Frame 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Measure Type: Number
Unit of Measure: percentage of participants
HbA1c <= 6.5 50.7 16.7
HbA1c < 7.0 69.3 35.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.66
Confidence Interval (2-Sided) 95%
3.70 to 12.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 5.71
Confidence Interval (2-Sided) 95%
3.35 to 9.73
Estimation Comments [Not Specified]
13.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Measure Type: Number
Unit of Measure: percentage of participants
40.7 16.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.17
Confidence Interval (2-Sided) 95%
2.32 to 7.47
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Participants Achieving HbA1c Target of <7.0% at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)
Hide Description 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.
Time Frame 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Measure Type: Number
Unit of Measure: percentage of participants
52.0 28.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.61
Confidence Interval (2-Sided) 95%
2.09 to 6.23
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 kg)
Hide Description [Not Specified]
Time Frame 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Measure Type: Number
Unit of Measure: percentage of participants
52.7 20.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dulaglutide + Insulin Glargine, Placebo + Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.60
Confidence Interval (2-Sided) 95%
3.26 to 9.62
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Rate of Hypoglycemic Events up to 28 Weeks
Hide Description 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.
Time Frame Baseline through 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description:

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 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

Overall Number of Participants Analyzed 150 150
Mean (Standard Deviation)
Unit of Measure: rate of hypoglycemic events per 30 days
0.63  (1.24) 0.70  (1.32)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Hide Arm/Group Description

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 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

All-Cause Mortality
Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/150 (6.00%)      7/150 (4.67%)    
Cardiac disorders     
Angina unstable  1  1/150 (0.67%)  1 1/150 (0.67%)  1
Atrial fibrillation  1  1/150 (0.67%)  1 0/150 (0.00%)  0
Bradycardia  1  2/150 (1.33%)  2 0/150 (0.00%)  0
Coronary artery disease  1  1/150 (0.67%)  1 0/150 (0.00%)  0
Myocardial infarction  1  1/150 (0.67%)  1 0/150 (0.00%)  0
General disorders     
Non-cardiac chest pain  1  0/150 (0.00%)  0 1/150 (0.67%)  1
Hepatobiliary disorders     
Granulomatous liver disease  1  1/150 (0.67%)  1 0/150 (0.00%)  0
Infections and infestations     
Gastroenteritis  1  1/150 (0.67%)  1 0/150 (0.00%)  0
Viral infection  1  0/150 (0.00%)  0 1/150 (0.67%)  1
Injury, poisoning and procedural complications     
Lower limb fracture  1  1/150 (0.67%)  1 0/150 (0.00%)  0
Metabolism and nutrition disorders     
Hypoglycaemia  1  1/150 (0.67%)  1 0/150 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  0/150 (0.00%)  0 1/150 (0.67%)  1
Osteoarthritis  1  0/150 (0.00%)  0 1/150 (0.67%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hepatic cancer  1  0/150 (0.00%)  0 1/150 (0.67%)  1
Nervous system disorders     
Carotid artery stenosis  1  1/150 (0.67%)  1 0/150 (0.00%)  0
Cerebral infarction  1  1/150 (0.67%)  1 0/150 (0.00%)  0
Transient ischaemic attack  1  2/150 (1.33%)  2 0/150 (0.00%)  0
Skin and subcutaneous tissue disorders     
Skin ulcer  1  0/150 (0.00%)  0 1/150 (0.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dulaglutide + Insulin Glargine Placebo + Insulin Glargine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   51/150 (34.00%)      29/150 (19.33%)    
Gastrointestinal disorders     
Diarrhoea  1  17/150 (11.33%)  19 6/150 (4.00%)  6
Dyspepsia  1  9/150 (6.00%)  9 0/150 (0.00%)  0
Nausea  1  18/150 (12.00%)  23 2/150 (1.33%)  3
Vomiting  1  9/150 (6.00%)  11 0/150 (0.00%)  0
Infections and infestations     
Nasopharyngitis  1  6/150 (4.00%)  7 14/150 (9.33%)  19
Upper respiratory tract infection  1  11/150 (7.33%)  18 10/150 (6.67%)  10
Metabolism and nutrition disorders     
Decreased appetite  1  10/150 (6.67%)  11 0/150 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 1-800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02152371     History of Changes
Other Study ID Numbers: 13195
H9X-MC-GBDI ( Other Identifier: Eli Lilly and Company )
2012-004229-25 ( EudraCT Number )
First Submitted: May 28, 2014
First Posted: June 2, 2014
Results First Submitted: October 12, 2016
Results First Posted: December 7, 2016
Last Update Posted: December 7, 2016