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Trial record 16 of 39 for:    LY2189265

A Study in Participants With Type 2 Diabetes Mellitus (AWARD-3)

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: NCT01126580
Recruitment Status : Completed
First Posted : May 19, 2010
Results First Posted : January 16, 2015
Last Update Posted : January 16, 2015
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Metformin
Drug: LY2189265
Drug: Placebo (oral)
Drug: Placebo (subcutaneous)
Enrollment 807

Recruitment Details  
Pre-assignment Details  
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Period Title: Overall Study
Started 269 270 268
Received at Least 1 Dose of Study Drug 269 270 268
Completed 26 Weeks 233 242 226
Completed 220 218 213
Not Completed 49 52 55
Reason Not Completed
Adverse Event             14             8             12
Withdrawal by Subject             11             19             14
Sponsor Decision             5             4             7
Physician Decision             1             1             2
Entry Criteria Not Met             1             1             2
Lack of Efficacy             2             3             4
Protocol Violation             0             1             2
Lost to Follow-up             15             13             9
Treatment Non-compliance             0             2             3
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin Total
Hide Arm/Group Description

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Total of all reporting groups
Overall Number of Baseline Participants 269 270 268 807
Hide Baseline Analysis Population Description
Participants who received at least 1 dose of LY2189265 or Metformin.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 269 participants 270 participants 268 participants 807 participants
55.51  (10.38) 55.90  (10.68) 55.26  (10.10) 55.56  (10.38)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 269 participants 270 participants 268 participants 807 participants
Female
155
  57.6%
152
  56.3%
147
  54.9%
454
  56.3%
Male
114
  42.4%
118
  43.7%
121
  45.1%
353
  43.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 269 participants 270 participants 268 participants 807 participants
Hispanic or Latino
90
  33.5%
87
  32.2%
95
  35.4%
272
  33.7%
Not Hispanic or Latino
179
  66.5%
183
  67.8%
173
  64.6%
535
  66.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 269 participants 270 participants 268 participants 807 participants
American Indian or Alaska Native
29
  10.8%
28
  10.4%
28
  10.4%
85
  10.5%
Asian
21
   7.8%
20
   7.4%
20
   7.5%
61
   7.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   0.4%
1
   0.1%
Black or African American
17
   6.3%
22
   8.1%
14
   5.2%
53
   6.6%
White
201
  74.7%
198
  73.3%
201
  75.0%
600
  74.3%
More than one race
1
   0.4%
2
   0.7%
4
   1.5%
7
   0.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 269 participants 270 participants 268 participants 807 participants
United States 77 80 74 231
Slovakia 8 9 9 26
Finland 3 5 4 12
Spain 12 11 12 35
United Kingdom 0 1 1 2
India 9 11 9 29
France 12 12 13 37
Czech Republic 10 9 8 27
Mexico 24 25 23 72
Canada 10 9 11 30
Puerto Rico 14 10 15 39
Argentina 27 27 26 80
Poland 7 6 5 18
Brazil 2 2 3 7
Croatia 3 4 4 11
Romania 14 13 13 40
South Africa 12 11 12 35
Germany 22 21 21 64
Korea, Republic of 3 4 5 12
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 269 participants 270 participants 268 participants 807 participants
92.67  (18.79) 91.79  (18.67) 92.40  (19.23) 92.28  (18.87)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms per square meter (kg/m^2)
Number Analyzed 269 participants 270 participants 268 participants 807 participants
33.66  (5.65) 33.08  (5.84) 33.05  (5.06) 33.26  (5.53)
[1]
Measure Description: Body mass index is an estimate of body fat based on body weight divided by height squared.
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 269 participants 270 participants 268 participants 807 participants
2.65  (1.50) 2.60  (2.17) 2.63  (1.77) 2.63  (1.83)
Glycosylated Hemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of glycosylated hemoglobin
Number Analyzed 269 participants 270 participants 268 participants 807 participants
7.63  (0.92) 7.58  (0.87) 7.60  (0.82) 7.60  (0.87)
1.Primary Outcome
Title Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Hide Description Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group (previous oral antihyperglycemic medication [OAM] versus no previous OAM) as fixed effects and baseline HbA1c as a covariate.
Time Frame Baseline, 26 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable HbA1c data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 265 265 265
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
-0.78  (0.06) -0.71  (0.06) -0.56  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments The study was designed with 90% power to detect non-inferiority of 1.5 mg LY2189265 vs Metformin on HbA1c change from baseline at the 26-week primary endpoint with a margin of 0.4%, a standard deviation of 1.3%, and a 2-sided alpha of 0.05 assuming no true difference between treatments. This corresponds to 223 participants per arm, with an assumed drop-out rate of 11%.
Type of Statistical Test Non-Inferiority or Equivalence
Comments A non-inferiority margin of 0.4% was used.
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is adjusted for multiplicity using a tree-gatekeeping strategy. To determine significance, the p-value is compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-0.36 to -0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A non-inferiority margin of 0.4% was used.
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is adjusted for multiplicity using a tree-gatekeeping strategy. To determine significance, the p-value is compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.29 to -0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments Superiority analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments Tree gatekeeping strategy to control the family-wise Type I error rate was applied.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-0.36 to -0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments Superiority analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments Tree gatekeeping strategy to control the family-wise Type I error rate was applied.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.29 to -0.01
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Hide Description Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group (previous oral antihyperglycemic medication [OAM] versus no previous OAM) as fixed effects and baseline HbA1c as a covariate.
Time Frame Baseline, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable HbA1c data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 265 265 265
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated hemoglobin
-0.70  (0.07) -0.55  (0.07) -0.51  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A non-inferiority margin of 0.4% was used.
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is adjusted for multiplicity using a tree-gatekeeping strategy. To determine significance, the p-value is compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.35 to -0.02
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A non-inferiority margin of 0.4% was used.
Statistical Test of Hypothesis P-Value <0.001
Comments The p-value is adjusted for multiplicity using a tree-gatekeeping strategy. To determine significance, the p-value is compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.20 to 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments Superiority analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments Tree gatekeeping strategy to control the family-wise Type I error rate was applied.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.35 to -0.02
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments Superiority analysis.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.299
Comments Tree gatekeeping strategy to control the family-wise Type I error rate was applied.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.20 to 0.12
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks
Hide Description The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a logistic regression model with baseline, prior medication group, and treatment as factors included in the model.
Time Frame 26 weeks and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable HbA1c data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 265 265 265
Measure Type: Number
Unit of Measure: percentage of participants
HbA1c less than 7%, 26 weeks 61.5 62.6 53.6
HbA1c less than or equal to 6.5%, 26 weeks 46.0 40.0 29.8
HbA1c less than 7%, 52 weeks 60.0 53.2 48.3
HbA1c less than or equal to 6.5%, 52 weeks 42.3 34.7 28.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments Treatment comparison for HbA1c less than 7.0% at 26 weeks.
Method Regression, Logistic
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments Treatment comparison for HbA1c less than 7.0% at 26 weeks.
Method Regression, Logistic
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Treatment comparison for HbA1c less than or equal to 6.5% at 26 weeks.
Method Regression, Logistic
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments Treatment comparison for HbA1c less than or equal to 6.5% at 26 weeks.
Method Regression, Logistic
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Treatment comparison for HbA1c less than 7% at 52 weeks.
Method Regression, Logistic
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.269
Comments Treatment comparison for HbA1c less than 7% at 52 weeks.
Method Regression, Logistic
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Treatment comparison for HbA1c less than or equal to 6.5% at 52 weeks.
Method Regression, Logistic
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.134
Comments Treatment comparison for HbA1c less than or equal to 6.5% at 52 weeks.
Method Regression, Logistic
Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose
Hide Description Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable fasting blood glucose data. Only pre-rescue measurements were used.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 267 265 264
Least Squares Mean (Standard Error)
Unit of Measure: millimoles per liter (mmol/L)
26 weeks (n=244, 247, 245) -1.61  (0.13) -1.46  (0.13) -1.34  (0.13)
52 weeks (n=207, 210, 194) -1.56  (0.14) -1.00  (0.14) -1.15  (0.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.079
Comments Treatment comparison at 26 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.451
Comments Treatment comparison at 26 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments Treatment comparison at 52 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.402
Comments Treatment comparison at 52 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles
Hide Description The SMBG data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. Least Squares (LS) means of the mean of the 8 time points (daily mean) were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline daily mean as a covariate.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable SMBG data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 211 207 218
Least Squares Mean (Standard Error)
Unit of Measure: millimoles per liter (mmol/L)
26 weeks (n=195, 200, 211) -1.98  (0.15) -1.75  (0.14) -1.68  (0.14)
52 weeks (n=197, 200, 212) -1.99  (0.16) -1.71  (0.16) -1.58  (0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.061
Comments Treatment comparison at 26 weeks.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.647
Comments Treatment comparison at 26 weeks.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments Treatment comparison at 52 weeks.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.469
Comments Treatment comparison at 52 weeks.
Method ANCOVA
Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Body Weight
Hide Description Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline body weight as a covariate.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable body weight data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 269 270 268
Least Squares Mean (Standard Error)
Unit of Measure: kilograms (kg)
26 weeks (n=267, 269, 267) -2.29  (0.24) -1.36  (0.24) -2.22  (0.24)
52 weeks (n=267, 269, 267) -1.93  (0.29) -1.09  (0.29) -2.20  (0.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.811
Comments Treatment comparison at 26 weeks.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Treatment comparison at 26 weeks.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.440
Comments Treatment comparison at 52 weeks.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Treatment comparison at 52 weeks.
Method ANCOVA
Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI)
Hide Description Body mass index is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline BMI as a covariate.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable BMI data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 267 269 267
Least Squares Mean (Standard Error)
Unit of Measure: kilograms per meter squared (kg/m^2)
26 weeks -0.86  (0.09) -0.51  (0.09) -0.82  (0.09)
52 weeks -0.73  (0.11) -0.42  (0.10) -0.83  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.750
Comments Treatment comparison at 26 weeks.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Treatment comparison at 26 weeks.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.412
Comments Treatment comparison at 52 weeks.
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Treatment comparison at 52 weeks.
Method ANCOVA
Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function
Hide Description The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as percentages of a normal reference population (normal young adults). The normal reference populations were set at 100%. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline HOMA2 as a covariate, and participant as a random effect.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable HOMA2-%B or HOMA2-%S data. Only pre-rescue measurements were used.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 245 242 242
Least Squares Mean (Standard Error)
Unit of Measure: percentage of HOMA2
HOMA2-%B, 26 weeks (n=207, 207, 215) 36.55  (3.42) 28.96  (3.44) 14.11  (3.37)
HOMA2-%B, 52 weeks (n=179, 185, 170) 29.97  (3.46) 22.5  (3.46) 9.77  (3.51)
HOMA2-%S, 26 weeks (n=207, 207, 215) 0.95  (2.29) 2.71  (2.29) 9.99  (2.25)
HOMA2-%S, 52 weeks (n=179, 185, 170) 5.29  (2.43) 1.84  (2.43) 10.83  (2.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Treatment comparison of HOMA2-%B at 26 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Treatment comparison of HOMA2-%B at 26 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Treatment comparison of HOMA2-%B at 52 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Treatment comparison of HOMA2-%B at 52 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Treatment comparison of HOMA2-%S at 26 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments Treatment comparison of HOMA2-%S at 26 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 1.5 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.077
Comments Treatment comparison of HOMA2-%S at 52 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 0.75 mg LY2189265, Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments Treatment comparison of HOMA2-%S at 52 weeks.
Method Mixed Models Analysis
Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score
Hide Description The Impact of Weight on Activities of Daily Living (renamed the Ability to Perform Physical Activities of Daily Living [APPADL]) questionnaire contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = "not at all difficult" and 1 = "unable to do". The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable APPADL data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 266 268 266
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
26 weeks (n=247, 251, 247) 0.09  (0.33) 0.19  (0.32) 0.02  (0.32)
52 weeks (n=247, 252, 248) 0.39  (0.33) -0.05  (0.33) 0.28  (0.33)
10.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score
Hide Description The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable IW-SP data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 268 270 268
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
26 weeks (n=248, 254, 249) 0.72  (0.19) 0.63  (0.18) 0.79  (0.18)
52 weeks (n=249, 255, 250) 0.45  (0.19) 0.61  (0.19) 0.75  (0.19)
11.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version
Hide Description The Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) is used to assess participant treatment satisfaction at each study visit. The questionnaire consists of 8 items, 6 of which (1 and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. Scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from 0 (very dissatisfied) to 36 (very satisfied). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable DTSQs data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) used to impute missing postbaseline values. If there were no data after randomization, endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 266 267 267
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
26 weeks (n=244, 249, 241) 1.93  (0.39) 1.81  (0.38) 2.04  (0.39)
52 weeks (n=245, 251, 244) 1.82  (0.44) 1.29  (0.43) 1.94  (0.44)
12.Secondary Outcome
Title Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Change Version
Hide Description The Diabetes Treatment Satisfaction Questionnaire change (DTSQc) score is used to assess relative change in participant satisfaction from baseline. The questionnaire consists of 8 items, 6 of which (1 and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 (much less satisfied) to +18 (much more satisfied). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score.
Time Frame 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable DTSQc data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) used to impute missing postbaseline values. If there were no data after randomization, endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 230 235 230
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
12.92  (0.52) 12.73  (0.50) 12.58  (0.51)
13.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score
Hide Description The Diabetes Symptoms Checklist-revised (DSC-r) was designed to assess the presence and perceived burden of diabetes-related symptoms. Respondents were to consider troublesomeness of 34 symptoms on a 5-point scale ranging from 5=“extremely” to 1=“not at all.” For symptoms/side-effects not experienced, the item was scored as 0. Symptoms were grouped into the following subscales: psychology-fatigue, psychology-cognitive, neurology-pain, neurology-sensory, cardiology, ophthalmology, hypoglycemia, and hyperglycemia. Subscale scores were calculated as the sum of the given subscale divided by the total number of items in the scale. Total score was computed from the sum of the 8 subscales and ranged from 0 to 40. Higher scores indicate greater symptom burden. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable DSC-r data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 267 270 267
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
26 weeks (n=245, 253, 248) 0.24  (0.36) -0.16  (0.35) 0.41  (0.35)
52 weeks (n=247, 255, 249) 0.49  (0.39) 0.42  (0.39) 0.59  (0.39)
14.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks
Hide Description A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 26 and 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame 26 weeks and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 269 270 268
Measure Type: Number
Unit of Measure: participants
26 weeks 163 150 151
52 weeks 179 177 170
15.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
Hide Description The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable ECG QTcF interval or PR interval data.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 269 270 268
Least Squares Mean (Standard Error)
Unit of Measure: milliseconds (msec)
QTcF interval, 26 weeks (n=230, 237, 221) 2.60  (1.17) 1.38  (1.16) -0.91  (1.18)
QTcF interval, 52 weeks (n=212, 212, 205) 3.76  (1.20) 0.73  (1.19) -0.53  (1.21)
PR interval, 26 weeks (n=226, 235, 218) -0.04  (1.12) -0.01  (1.10) -2.04  (1.13)
PR interval, 52 weeks (n=209, 210, 201) 1.15  (1.18) 1.53  (1.17) -2.88  (1.19)
16.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate
Hide Description Electrocardiogram (ECG) heart rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects and baseline interval as a covariate.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable ECG heart rate data.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 267 268 264
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute (bpm)
26 weeks (n=230, 237, 221) 1.60  (0.60) 2.57  (0.59) 0.82  (0.61)
52 weeks (n=212, 212, 205) 2.02  (0.66) 2.36  (0.66) 1.27  (0.67)
17.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Pulse Rate
Hide Description Sitting pulse rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable pulse rate data.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 269 270 268
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute (bpm)
26 weeks (n=244, 251, 239) 2.39  (0.58) 2.14  (0.57) 1.59  (0.58)
52 weeks (n=221, 219, 215) 1.84  (0.57) 1.63  (0.57) 1.12  (0.57)
18.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Blood Pressure
Hide Description Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable blood pressure data.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 269 270 268
Least Squares Mean (Standard Error)
Unit of Measure: milliliters of mercury (mmHg)
SBP, 26 weeks (n=244, 251, 239) -1.89  (0.89) -2.61  (0.88) -0.91  (0.89)
SBP, 52 weeks (n=221, 219, 215) -0.11  (0.88) -2.74  (0.88) -0.98  (0.88)
DBP, 26 weeks (n=244, 251, 239) 0.05  (0.57) -1.02  (0.56) -0.64  (0.58)
DBP, 52 weeks (n=221, 219, 215) 0.31  (0.60) -1.37  (0.59) -0.38  (0.60)
19.Secondary Outcome
Title Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol
Hide Description Percent changes in total cholesterol were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable cholesterol data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 258 257 256
Median (Inter-Quartile Range)
Unit of Measure: percentage change in total cholesterol
26 weeks (n=244, 244, 243)
-3.86
(-10.83 to 5.24)
-1.77
(-9.78 to 7.57)
-3.51
(-12.19 to 5.45)
52 weeks (n=247, 248, 245)
-1.69
(-11.11 to 7.45)
-0.78
(-10.02 to 8.10)
-3.88
(-12.14 to 5.69)
20.Secondary Outcome
Title Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C)
Hide Description Percentage changes in HDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable HDL-C data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 259 257 257
Median (Inter-Quartile Range)
Unit of Measure: percentage change in HDL-C
26 weeks (n=246, 244, 244)
2.39
(-4.11 to 13.54)
4.20
(-5.66 to 14.66)
5.78
(-2.66 to 14.13)
52 weeks (n=248, 248, 246)
4.95
(-4.55 to 13.17)
2.31
(-5.16 to 12.56)
4.32
(-6.56 to 13.64)
21.Secondary Outcome
Title Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C)
Hide Description Percentage changes in LDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable LDL-C data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 249 249 243
Median (Inter-Quartile Range)
Unit of Measure: percentage change in LDL-C
26 weeks (n=233, 231, 221)
-6.86
(-18.26 to 8.20)
-2.70
(-15.33 to 9.15)
-8.97
(-20.21 to 5.00)
52 weeks (n=236, 240, 231)
-2.06
(-15.93 to 9.31)
-2.34
(-15.22 to 10.56)
-7.23
(-18.56 to 4.36)
22.Secondary Outcome
Title Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides
Hide Description Percentage changes in triglycerides were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable triglyceride data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 266 265 265
Median (Inter-Quartile Range)
Unit of Measure: percentage change in triglycerides
26 weeks (n=252, 252, 253)
-2.35
(-22.32 to 13.61)
-1.96
(-21.66 to 22.63)
2.56
(-16.00 to 23.79)
52 weeks (n=255, 256, 254)
-4.27
(-22.91 to 19.23)
-0.86
(-22.31 to 25.37)
1.91
(-21.65 to 24.04)
23.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes
Hide Description Amylase (total and pancreas-derived [PD]) and lipase concentrations were measured.
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable pancreatic enzyme data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 266 267 267
Median (Inter-Quartile Range)
Unit of Measure: units per liter (U/L)
Amylase (total), 26 weeks
7.00
(2.00 to 13.00)
6.00
(0.00 to 13.00)
4.00
(-2.00 to 10.00)
Amylase (total), 52 weeks
5.50
(-1.00 to 13.00)
5.00
(-1.00 to 13.00)
4.00
(-2.00 to 9.00)
Amylase (PD), 26 weeks
5.00
(2.00 to 9.00)
4.00
(1.00 to 7.00)
1.00
(-1.00 to 5.00)
Amylase (PD), 52 weeks
4.00
(1.00 to 7.00)
3.00
(0.00 to 8.00)
2.00
(-1.00 to 5.00)
Lipase, 26 weeks
7.00
(1.00 to 16.00)
5.00
(0.00 to 13.00)
1.00
(-4.00 to 8.00)
Lipase, 52 weeks
5.00
(-1.00 to 13.00)
5.00
(0.00 to 12.00)
1.00
(-4.00 to 6.00)
24.Secondary Outcome
Title Change From Baseline to 26 and 52 Weeks in Serum Calcitonin
Hide Description [Not Specified]
Time Frame Baseline, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin with evaluable serum calcitonin data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 266 267 267
Median (Inter-Quartile Range)
Unit of Measure: picograms per milliliter (pcg/mL)
26 weeks
0.00
(0.00 to 0.00)
0.00
(0.00 to 0.00)
0.00
(0.00 to 0.00)
52 weeks
0.00
(0.00 to 0.00)
0.00
(0.00 to 0.00)
0.00
(0.00 to 0.00)
25.Secondary Outcome
Title Number of Participants With Treatment Emergent Anti-LY2189265 Antibodies
Time Frame Baseline through 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 with evaluable LY2189265 ADA data.
Arm/Group Title 1.5 mg or 0.75 mg LY2189265
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg) or 0.75 mg, subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Overall Number of Participants Analyzed 521
Measure Type: Number
Unit of Measure: participants
10
26.Secondary Outcome
Title Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks
Hide Description Hypoglycemic events 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 less than or equal to 70 milligrams per deciliter [mg/dL]), or asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 70 mg/dL). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame Baseline through 26 weeks and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin. Only pre-rescue measurements were used.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 269 270 268
Measure Type: Number
Unit of Measure: events
Severe, 26 weeks (n=241, 248, 236) 0 0 0
Severe, 52 weeks (n=214, 217, 199) 0 0 0
Documented Symptomatic, 26 weeks (n=241, 248, 236) 2 6 2
Documented Symptomatic, 52 weeks (n=214, 217, 199) 7 8 2
Asymptomatic, 26 weeks (n=241, 248, 236) 19 9 13
Asymptomatic, 52 weeks (n=214, 217, 199) 5 9 9
27.Secondary Outcome
Title Rate of Self-reported Hypoglycemic Events at 52 Weeks
Hide Description Hypoglycemic events 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 less than or equal to 70 milligrams per deciliter [mg/dL]), or asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 70 mg/dL). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame Baseline through 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin. Only pre-rescue measurements were used.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 269 270 268
Mean (Standard Deviation)
Unit of Measure: events per participant per year
Severe 0.00  (0.00) 0.00  (0.00) 0.00  (0.00)
Documented Symptomatic 0.62  (8.91) 0.15  (0.72) 0.09  (0.50)
Asymptomatic 0.24  (1.26) 0.30  (1.85) 0.18  (0.79)
28.Secondary Outcome
Title Number of Participants With Adjudicated Pancreatitis at 52 Weeks Plus 30-day Follow up
Hide Description The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 52 weeks plus 30-day follow up. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame Baseline through 52 weeks plus 30-day follow up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin. Only pre-rescue measurements were used.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 269 270 268
Measure Type: Number
Unit of Measure: participants
0 0 0
29.Secondary Outcome
Title Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up
Hide Description Information on cardiovascular (CV) risk factors was collected at baseline. Data on any new CV event was prospectively collected using a CV event electronic case report form. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by an external committee of physicians with cardiology expertise. Nonfatal cardiovascular AEs to be adjudicated included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions, and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with CV events confirmed by adjudication is summarized cumulatively at 52 weeks plus 30-day follow up. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module.
Time Frame Baseline through 52 weeks plus 30-day follow up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 or Metformin.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

Overall Number of Participants Analyzed 269 270 268
Measure Type: Number
Unit of Measure: participants
Any CV Event 1 2 1
Any Fatal CV Event 0 0 0
Any Nonfatal CV Event 1 2 1
30.Secondary Outcome
Title Measurement of LY2189265 Drug Concentration for Pharmacokinetics: Area Under the Concentration Curve (AUC)
Hide Description Evaluable pharmacokinetic concentrations from the 4-week, 13-week, 26-week, and 52-week timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.
Time Frame 4 weeks, 13 weeks, 26 weeks, and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of LY2189265 with evaluable LY2189265 concentration data.
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265
Hide Arm/Group Description:

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Overall Number of Participants Analyzed 144 146
Mean (Standard Deviation)
Unit of Measure: nanogram hours per milliliter (ng*hr/mL)
12036  (5385) 5919  (1548)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Hide Arm/Group Description

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks

Placebo: orally, twice daily for 52 weeks

Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks

Placebo: subcutaneously (SC), once weekly for 52 weeks

All-Cause Mortality
1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/269 (5.58%)      20/270 (7.41%)      16/268 (5.97%)    
Cardiac disorders       
Acute myocardial infarction  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Angina pectoris  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Angina unstable  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Atrial fibrillation  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Cardiac failure  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Cardiac failure congestive  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  2
Coronary artery stenosis  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Pericardial effusion  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Gastrointestinal disorders       
Abdominal pain  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Colitis  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Constipation  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Diarrhoea haemorrhagic  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Dysphagia  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Hiatus hernia  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Ileus  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Oesophageal spasm  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
General disorders       
Chest pain  1  0/269 (0.00%)  0 3/270 (1.11%)  3 0/268 (0.00%)  0
Paradoxical drug reaction  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Hepatobiliary disorders       
Cholecystitis acute  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Cholecystitis chronic  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Cholelithiasis  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Gallbladder disorder  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Infections and infestations       
Abdominal abscess  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Appendicitis  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Cellulitis  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Cholecystitis infective  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Disseminated tuberculosis  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Echinococciasis  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Gastroenteritis  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Hepatic echinococciasis  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Pharyngeal abscess  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Pneumonia  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Pyelonephritis acute  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Urinary tract infection  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Injury, poisoning and procedural complications       
Alcohol poisoning  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Fall  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Humerus fracture  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Meniscus lesion  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Intervertebral disc protrusion  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Musculoskeletal chest pain  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Osteoarthritis  1  1/269 (0.37%)  1 2/270 (0.74%)  2 0/268 (0.00%)  0
Osteonecrosis  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Spinal column stenosis  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Non-hodgkin's lymphoma  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Ovarian fibroma  1  0/155 (0.00%)  0 0/152 (0.00%)  0 1/147 (0.68%)  1
Tongue carcinoma stage I  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Nervous system disorders       
Cerebral infarction  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Convulsion  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Hypoaesthesia  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Presyncope  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Syncope  1  0/269 (0.00%)  0 2/270 (0.74%)  2 0/268 (0.00%)  0
Transient ischaemic attack  1  1/269 (0.37%)  1 0/270 (0.00%)  0 1/268 (0.37%)  1
VIth nerve paralysis  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Pregnancy, puerperium and perinatal conditions       
Pregnancy  1  1/155 (0.65%)  1 0/152 (0.00%)  0 0/147 (0.00%)  0
Psychiatric disorders       
Bipolar II disorder  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  2
Suicidal ideation  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Renal and urinary disorders       
Nephrolithiasis  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Bronchospasm  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  2
Haemoptysis  1  0/269 (0.00%)  0 1/270 (0.37%)  1 0/268 (0.00%)  0
Nasal polyps  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Nasal septum deviation  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Nasal turbinate hypertrophy  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Pleural effusion  1  0/269 (0.00%)  0 0/270 (0.00%)  0 1/268 (0.37%)  1
Vascular disorders       
Hypertension  1  1/269 (0.37%)  1 0/270 (0.00%)  0 0/268 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
1.5 mg LY2189265 0.75 mg LY2189265 Metformin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   177/269 (65.80%)      178/270 (65.93%)      170/268 (63.43%)    
Gastrointestinal disorders       
Abdominal distension  1  13/269 (4.83%)  18 13/270 (4.81%)  19 10/268 (3.73%)  14
Abdominal pain  1  11/269 (4.09%)  16 10/270 (3.70%)  11 6/268 (2.24%)  7
Constipation  1  18/269 (6.69%)  23 12/270 (4.44%)  13 3/268 (1.12%)  3
Diarrhoea  1  31/269 (11.52%)  37 26/270 (9.63%)  30 39/268 (14.55%)  44
Dyspepsia  1  12/269 (4.46%)  15 8/270 (2.96%)  22 6/268 (2.24%)  7
Nausea  1  53/269 (19.70%)  76 31/270 (11.48%)  45 43/268 (16.04%)  50
Vomiting  1  26/269 (9.67%)  32 20/270 (7.41%)  24 14/268 (5.22%)  70
Infections and infestations       
Bronchitis  1  7/269 (2.60%)  8 11/270 (4.07%)  11 9/268 (3.36%)  9
Influenza  1  9/269 (3.35%)  11 11/270 (4.07%)  14 8/268 (2.99%)  13
Nasopharyngitis  1  14/269 (5.20%)  16 9/270 (3.33%)  10 28/268 (10.45%)  39
Upper respiratory tract infection  1  16/269 (5.95%)  16 17/270 (6.30%)  20 8/268 (2.99%)  10
Urinary tract infection  1  10/269 (3.72%)  11 11/270 (4.07%)  13 6/268 (2.24%)  7
Metabolism and nutrition disorders       
Decreased appetite  1  18/269 (6.69%)  22 12/270 (4.44%)  15 12/268 (4.48%)  14
Musculoskeletal and connective tissue disorders       
Back pain  1  5/269 (1.86%)  5 9/270 (3.33%)  11 12/268 (4.48%)  13
Nervous system disorders       
Dizziness  1  5/269 (1.86%)  6 12/270 (4.44%)  13 9/268 (3.36%)  12
Headache  1  10/269 (3.72%)  14 14/270 (5.19%)  57 20/268 (7.46%)  28
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
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: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01126580     History of Changes
Other Study ID Numbers: 11375
H9X-MC-GBDC ( Other Identifier: Eli Lilly and Company )
CTRI/2010/091/003036 ( Registry Identifier: Clinical Trials Register India )
First Submitted: May 18, 2010
First Posted: May 19, 2010
Results First Submitted: October 3, 2014
Results First Posted: January 16, 2015
Last Update Posted: January 16, 2015