Trial Outcomes & Findings for A Study in Participants With Type 2 Diabetes Mellitus (AWARD-3) (NCT NCT01126580)
NCT ID: NCT01126580
Last Updated: 2015-01-16
Results Overview
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.
COMPLETED
PHASE3
807 participants
Baseline, 26 weeks
2015-01-16
Participant Flow
Participant milestones
| Measure |
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
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 Study
STARTED
|
269
|
270
|
268
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
269
|
270
|
268
|
|
Overall Study
Completed 26 Weeks
|
233
|
242
|
226
|
|
Overall Study
COMPLETED
|
220
|
218
|
213
|
|
Overall Study
NOT COMPLETED
|
49
|
52
|
55
|
Reasons for withdrawal
| Measure |
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
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 Study
Adverse Event
|
14
|
8
|
12
|
|
Overall Study
Withdrawal by Subject
|
11
|
19
|
14
|
|
Overall Study
Sponsor Decision
|
5
|
4
|
7
|
|
Overall Study
Physician Decision
|
1
|
1
|
2
|
|
Overall Study
Entry Criteria Not Met
|
1
|
1
|
2
|
|
Overall Study
Lack of Efficacy
|
2
|
3
|
4
|
|
Overall Study
Protocol Violation
|
0
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
15
|
13
|
9
|
|
Overall Study
Treatment Non-compliance
|
0
|
2
|
3
|
Baseline Characteristics
A Study in Participants With Type 2 Diabetes Mellitus (AWARD-3)
Baseline characteristics by cohort
| Measure |
1.5 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
n=807 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
55.51 years
STANDARD_DEVIATION 10.38 • n=93 Participants
|
55.90 years
STANDARD_DEVIATION 10.68 • n=4 Participants
|
55.26 years
STANDARD_DEVIATION 10.10 • n=27 Participants
|
55.56 years
STANDARD_DEVIATION 10.38 • n=483 Participants
|
|
Sex: Female, Male
Female
|
155 Participants
n=93 Participants
|
152 Participants
n=4 Participants
|
147 Participants
n=27 Participants
|
454 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
114 Participants
n=93 Participants
|
118 Participants
n=4 Participants
|
121 Participants
n=27 Participants
|
353 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
90 Participants
n=93 Participants
|
87 Participants
n=4 Participants
|
95 Participants
n=27 Participants
|
272 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
179 Participants
n=93 Participants
|
183 Participants
n=4 Participants
|
173 Participants
n=27 Participants
|
535 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
29 Participants
n=93 Participants
|
28 Participants
n=4 Participants
|
28 Participants
n=27 Participants
|
85 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
21 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
61 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
17 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
53 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
201 Participants
n=93 Participants
|
198 Participants
n=4 Participants
|
201 Participants
n=27 Participants
|
600 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
77 participants
n=93 Participants
|
80 participants
n=4 Participants
|
74 participants
n=27 Participants
|
231 participants
n=483 Participants
|
|
Region of Enrollment
Slovakia
|
8 participants
n=93 Participants
|
9 participants
n=4 Participants
|
9 participants
n=27 Participants
|
26 participants
n=483 Participants
|
|
Region of Enrollment
Finland
|
3 participants
n=93 Participants
|
5 participants
n=4 Participants
|
4 participants
n=27 Participants
|
12 participants
n=483 Participants
|
|
Region of Enrollment
Spain
|
12 participants
n=93 Participants
|
11 participants
n=4 Participants
|
12 participants
n=27 Participants
|
35 participants
n=483 Participants
|
|
Region of Enrollment
United Kingdom
|
0 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
2 participants
n=483 Participants
|
|
Region of Enrollment
India
|
9 participants
n=93 Participants
|
11 participants
n=4 Participants
|
9 participants
n=27 Participants
|
29 participants
n=483 Participants
|
|
Region of Enrollment
France
|
12 participants
n=93 Participants
|
12 participants
n=4 Participants
|
13 participants
n=27 Participants
|
37 participants
n=483 Participants
|
|
Region of Enrollment
Czech Republic
|
10 participants
n=93 Participants
|
9 participants
n=4 Participants
|
8 participants
n=27 Participants
|
27 participants
n=483 Participants
|
|
Region of Enrollment
Mexico
|
24 participants
n=93 Participants
|
25 participants
n=4 Participants
|
23 participants
n=27 Participants
|
72 participants
n=483 Participants
|
|
Region of Enrollment
Canada
|
10 participants
n=93 Participants
|
9 participants
n=4 Participants
|
11 participants
n=27 Participants
|
30 participants
n=483 Participants
|
|
Region of Enrollment
Puerto Rico
|
14 participants
n=93 Participants
|
10 participants
n=4 Participants
|
15 participants
n=27 Participants
|
39 participants
n=483 Participants
|
|
Region of Enrollment
Argentina
|
27 participants
n=93 Participants
|
27 participants
n=4 Participants
|
26 participants
n=27 Participants
|
80 participants
n=483 Participants
|
|
Region of Enrollment
Poland
|
7 participants
n=93 Participants
|
6 participants
n=4 Participants
|
5 participants
n=27 Participants
|
18 participants
n=483 Participants
|
|
Region of Enrollment
Brazil
|
2 participants
n=93 Participants
|
2 participants
n=4 Participants
|
3 participants
n=27 Participants
|
7 participants
n=483 Participants
|
|
Region of Enrollment
Croatia
|
3 participants
n=93 Participants
|
4 participants
n=4 Participants
|
4 participants
n=27 Participants
|
11 participants
n=483 Participants
|
|
Region of Enrollment
Romania
|
14 participants
n=93 Participants
|
13 participants
n=4 Participants
|
13 participants
n=27 Participants
|
40 participants
n=483 Participants
|
|
Region of Enrollment
South Africa
|
12 participants
n=93 Participants
|
11 participants
n=4 Participants
|
12 participants
n=27 Participants
|
35 participants
n=483 Participants
|
|
Region of Enrollment
Germany
|
22 participants
n=93 Participants
|
21 participants
n=4 Participants
|
21 participants
n=27 Participants
|
64 participants
n=483 Participants
|
|
Region of Enrollment
Korea, Republic of
|
3 participants
n=93 Participants
|
4 participants
n=4 Participants
|
5 participants
n=27 Participants
|
12 participants
n=483 Participants
|
|
Body Weight
|
92.67 kilograms (kg)
STANDARD_DEVIATION 18.79 • n=93 Participants
|
91.79 kilograms (kg)
STANDARD_DEVIATION 18.67 • n=4 Participants
|
92.40 kilograms (kg)
STANDARD_DEVIATION 19.23 • n=27 Participants
|
92.28 kilograms (kg)
STANDARD_DEVIATION 18.87 • n=483 Participants
|
|
Body Mass Index (BMI)
|
33.66 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 5.65 • n=93 Participants
|
33.08 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 5.84 • n=4 Participants
|
33.05 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 5.06 • n=27 Participants
|
33.26 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 5.53 • n=483 Participants
|
|
Duration of Diabetes
|
2.65 years
STANDARD_DEVIATION 1.50 • n=93 Participants
|
2.60 years
STANDARD_DEVIATION 2.17 • n=4 Participants
|
2.63 years
STANDARD_DEVIATION 1.77 • n=27 Participants
|
2.63 years
STANDARD_DEVIATION 1.83 • n=483 Participants
|
|
Glycosylated Hemoglobin (HbA1c)
|
7.63 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.92 • n=93 Participants
|
7.58 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.87 • n=4 Participants
|
7.60 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.82 • n=27 Participants
|
7.60 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 0.87 • n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline, 26 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=265 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=265 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=265 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)
|
-0.78 percentage of glycosylated hemoglobin
Standard Error 0.06
|
-0.71 percentage of glycosylated hemoglobin
Standard Error 0.06
|
-0.56 percentage of glycosylated hemoglobin
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Baseline, 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=265 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=265 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=265 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)
|
-0.70 percentage of glycosylated hemoglobin
Standard Error 0.07
|
-0.55 percentage of glycosylated hemoglobin
Standard Error 0.07
|
-0.51 percentage of glycosylated hemoglobin
Standard Error 0.07
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=265 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=265 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=265 Participants
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
|
|---|---|---|---|
|
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
HbA1c less than 7%, 26 weeks
|
61.5 percentage of participants
|
62.6 percentage of participants
|
53.6 percentage of participants
|
|
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
HbA1c less than or equal to 6.5%, 26 weeks
|
46.0 percentage of participants
|
40.0 percentage of participants
|
29.8 percentage of participants
|
|
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
HbA1c less than 7%, 52 weeks
|
60.0 percentage of participants
|
53.2 percentage of participants
|
48.3 percentage of participants
|
|
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
HbA1c less than or equal to 6.5%, 52 weeks
|
42.3 percentage of participants
|
34.7 percentage of participants
|
28.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: Participants who received at least one dose of LY2189265 or Metformin with evaluable fasting blood glucose data. Only pre-rescue measurements were used.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=267 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=265 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=264 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose
26 weeks (n=244, 247, 245)
|
-1.61 millimoles per liter (mmol/L)
Standard Error 0.13
|
-1.46 millimoles per liter (mmol/L)
Standard Error 0.13
|
-1.34 millimoles per liter (mmol/L)
Standard Error 0.13
|
|
Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose
52 weeks (n=207, 210, 194)
|
-1.56 millimoles per liter (mmol/L)
Standard Error 0.14
|
-1.00 millimoles per liter (mmol/L)
Standard Error 0.14
|
-1.15 millimoles per liter (mmol/L)
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=211 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=207 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=218 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles
26 weeks (n=195, 200, 211)
|
-1.98 millimoles per liter (mmol/L)
Standard Error 0.15
|
-1.75 millimoles per liter (mmol/L)
Standard Error 0.14
|
-1.68 millimoles per liter (mmol/L)
Standard Error 0.14
|
|
Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles
52 weeks (n=197, 200, 212)
|
-1.99 millimoles per liter (mmol/L)
Standard Error 0.16
|
-1.71 millimoles per liter (mmol/L)
Standard Error 0.16
|
-1.58 millimoles per liter (mmol/L)
Standard Error 0.15
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Body Weight
52 weeks (n=267, 269, 267)
|
-1.93 kilograms (kg)
Standard Error 0.29
|
-1.09 kilograms (kg)
Standard Error 0.29
|
-2.20 kilograms (kg)
Standard Error 0.29
|
|
Change From Baseline to 26 and 52 Weeks in Body Weight
26 weeks (n=267, 269, 267)
|
-2.29 kilograms (kg)
Standard Error 0.24
|
-1.36 kilograms (kg)
Standard Error 0.24
|
-2.22 kilograms (kg)
Standard Error 0.24
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=267 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=267 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI)
52 weeks
|
-0.73 kilograms per meter squared (kg/m^2)
Standard Error 0.11
|
-0.42 kilograms per meter squared (kg/m^2)
Standard Error 0.10
|
-0.83 kilograms per meter squared (kg/m^2)
Standard Error 0.11
|
|
Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI)
26 weeks
|
-0.86 kilograms per meter squared (kg/m^2)
Standard Error 0.09
|
-0.51 kilograms per meter squared (kg/m^2)
Standard Error 0.09
|
-0.82 kilograms per meter squared (kg/m^2)
Standard Error 0.09
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=245 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=242 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=242 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function
HOMA2-%B, 26 weeks (n=207, 207, 215)
|
36.55 percentage of HOMA2
Standard Error 3.42
|
28.96 percentage of HOMA2
Standard Error 3.44
|
14.11 percentage of HOMA2
Standard Error 3.37
|
|
Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function
HOMA2-%B, 52 weeks (n=179, 185, 170)
|
29.97 percentage of HOMA2
Standard Error 3.46
|
22.5 percentage of HOMA2
Standard Error 3.46
|
9.77 percentage of HOMA2
Standard Error 3.51
|
|
Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function
HOMA2-%S, 26 weeks (n=207, 207, 215)
|
0.95 percentage of HOMA2
Standard Error 2.29
|
2.71 percentage of HOMA2
Standard Error 2.29
|
9.99 percentage of HOMA2
Standard Error 2.25
|
|
Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function
HOMA2-%S, 52 weeks (n=179, 185, 170)
|
5.29 percentage of HOMA2
Standard Error 2.43
|
1.84 percentage of HOMA2
Standard Error 2.43
|
10.83 percentage of HOMA2
Standard Error 2.48
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=266 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=268 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=266 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score
26 weeks (n=247, 251, 247)
|
0.09 units on a scale
Standard Error 0.33
|
0.19 units on a scale
Standard Error 0.32
|
0.02 units on a scale
Standard Error 0.32
|
|
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score
52 weeks (n=247, 252, 248)
|
0.39 units on a scale
Standard Error 0.33
|
-0.05 units on a scale
Standard Error 0.33
|
0.28 units on a scale
Standard Error 0.33
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=268 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score
52 weeks (n=249, 255, 250)
|
0.45 units on a scale
Standard Error 0.19
|
0.61 units on a scale
Standard Error 0.19
|
0.75 units on a scale
Standard Error 0.19
|
|
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score
26 weeks (n=248, 254, 249)
|
0.72 units on a scale
Standard Error 0.19
|
0.63 units on a scale
Standard Error 0.18
|
0.79 units on a scale
Standard Error 0.18
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=266 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=267 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=267 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version
26 weeks (n=244, 249, 241)
|
1.93 units on a scale
Standard Error 0.39
|
1.81 units on a scale
Standard Error 0.38
|
2.04 units on a scale
Standard Error 0.39
|
|
Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version
52 weeks (n=245, 251, 244)
|
1.82 units on a scale
Standard Error 0.44
|
1.29 units on a scale
Standard Error 0.43
|
1.94 units on a scale
Standard Error 0.44
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=230 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=235 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=230 Participants
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
|
|---|---|---|---|
|
Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Change Version
|
12.92 units on a scale
Standard Error 0.52
|
12.73 units on a scale
Standard Error 0.50
|
12.58 units on a scale
Standard Error 0.51
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=267 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=267 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score
26 weeks (n=245, 253, 248)
|
0.24 units on a scale
Standard Error 0.36
|
-0.16 units on a scale
Standard Error 0.35
|
0.41 units on a scale
Standard Error 0.35
|
|
Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score
52 weeks (n=247, 255, 249)
|
0.49 units on a scale
Standard Error 0.39
|
0.42 units on a scale
Standard Error 0.39
|
0.59 units on a scale
Standard Error 0.39
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeksPopulation: Participants who received at least one dose of LY2189265 or Metformin.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
|
|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks
26 weeks
|
163 participants
|
150 participants
|
151 participants
|
|
Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks
52 weeks
|
179 participants
|
177 participants
|
170 participants
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: Participants who received at least one dose of LY2189265 or Metformin with evaluable ECG QTcF interval or PR interval data.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
QTcF interval, 26 weeks (n=230, 237, 221)
|
2.60 milliseconds (msec)
Standard Error 1.17
|
1.38 milliseconds (msec)
Standard Error 1.16
|
-0.91 milliseconds (msec)
Standard Error 1.18
|
|
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
PR interval, 26 weeks (n=226, 235, 218)
|
-0.04 milliseconds (msec)
Standard Error 1.12
|
-0.01 milliseconds (msec)
Standard Error 1.10
|
-2.04 milliseconds (msec)
Standard Error 1.13
|
|
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
PR interval, 52 weeks (n=209, 210, 201)
|
1.15 milliseconds (msec)
Standard Error 1.18
|
1.53 milliseconds (msec)
Standard Error 1.17
|
-2.88 milliseconds (msec)
Standard Error 1.19
|
|
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
QTcF interval, 52 weeks (n=212, 212, 205)
|
3.76 milliseconds (msec)
Standard Error 1.20
|
0.73 milliseconds (msec)
Standard Error 1.19
|
-0.53 milliseconds (msec)
Standard Error 1.21
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: Participants who received at least one dose of LY2189265 or Metformin with evaluable ECG heart rate data.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=267 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=268 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=264 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate
52 weeks (n=212, 212, 205)
|
2.02 beats per minute (bpm)
Standard Error 0.66
|
2.36 beats per minute (bpm)
Standard Error 0.66
|
1.27 beats per minute (bpm)
Standard Error 0.67
|
|
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate
26 weeks (n=230, 237, 221)
|
1.60 beats per minute (bpm)
Standard Error 0.60
|
2.57 beats per minute (bpm)
Standard Error 0.59
|
0.82 beats per minute (bpm)
Standard Error 0.61
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: Participants who received at least one dose of LY2189265 or Metformin with evaluable pulse rate data.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Pulse Rate
26 weeks (n=244, 251, 239)
|
2.39 beats per minute (bpm)
Standard Error 0.58
|
2.14 beats per minute (bpm)
Standard Error 0.57
|
1.59 beats per minute (bpm)
Standard Error 0.58
|
|
Change From Baseline to 26 and 52 Weeks in Pulse Rate
52 weeks (n=221, 219, 215)
|
1.84 beats per minute (bpm)
Standard Error 0.57
|
1.63 beats per minute (bpm)
Standard Error 0.57
|
1.12 beats per minute (bpm)
Standard Error 0.57
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: Participants who received at least one dose of LY2189265 or Metformin with evaluable blood pressure data.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Blood Pressure
SBP, 26 weeks (n=244, 251, 239)
|
-1.89 milliliters of mercury (mmHg)
Standard Error 0.89
|
-2.61 milliliters of mercury (mmHg)
Standard Error 0.88
|
-0.91 milliliters of mercury (mmHg)
Standard Error 0.89
|
|
Change From Baseline to 26 and 52 Weeks in Blood Pressure
DBP, 26 weeks (n=244, 251, 239)
|
0.05 milliliters of mercury (mmHg)
Standard Error 0.57
|
-1.02 milliliters of mercury (mmHg)
Standard Error 0.56
|
-0.64 milliliters of mercury (mmHg)
Standard Error 0.58
|
|
Change From Baseline to 26 and 52 Weeks in Blood Pressure
DBP, 52 weeks (n=221, 219, 215)
|
0.31 milliliters of mercury (mmHg)
Standard Error 0.60
|
-1.37 milliliters of mercury (mmHg)
Standard Error 0.59
|
-0.38 milliliters of mercury (mmHg)
Standard Error 0.60
|
|
Change From Baseline to 26 and 52 Weeks in Blood Pressure
SBP, 52 weeks (n=221, 219, 215)
|
-0.11 milliliters of mercury (mmHg)
Standard Error 0.88
|
-2.74 milliliters of mercury (mmHg)
Standard Error 0.88
|
-0.98 milliliters of mercury (mmHg)
Standard Error 0.88
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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.
Percent changes in total cholesterol were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Outcome measures
| Measure |
1.5 mg LY2189265
n=258 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=257 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=256 Participants
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
|
|---|---|---|---|
|
Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol
26 weeks (n=244, 244, 243)
|
-3.86 percentage change in total cholesterol
Interval -10.83 to 5.24
|
-1.77 percentage change in total cholesterol
Interval -9.78 to 7.57
|
-3.51 percentage change in total cholesterol
Interval -12.19 to 5.45
|
|
Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol
52 weeks (n=247, 248, 245)
|
-1.69 percentage change in total cholesterol
Interval -11.11 to 7.45
|
-0.78 percentage change in total cholesterol
Interval -10.02 to 8.1
|
-3.88 percentage change in total cholesterol
Interval -12.14 to 5.69
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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
Percentage changes in HDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Outcome measures
| Measure |
1.5 mg LY2189265
n=259 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=257 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=257 Participants
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
|
|---|---|---|---|
|
Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C)
26 weeks (n=246, 244, 244)
|
2.39 percentage change in HDL-C
Interval -4.11 to 13.54
|
4.20 percentage change in HDL-C
Interval -5.66 to 14.66
|
5.78 percentage change in HDL-C
Interval -2.66 to 14.13
|
|
Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C)
52 weeks (n=248, 248, 246)
|
4.95 percentage change in HDL-C
Interval -4.55 to 13.17
|
2.31 percentage change in HDL-C
Interval -5.16 to 12.56
|
4.32 percentage change in HDL-C
Interval -6.56 to 13.64
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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
Percentage changes in LDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Outcome measures
| Measure |
1.5 mg LY2189265
n=249 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=249 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=243 Participants
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
|
|---|---|---|---|
|
Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C)
52 weeks (n=236, 240, 231)
|
-2.06 percentage change in LDL-C
Interval -15.93 to 9.31
|
-2.34 percentage change in LDL-C
Interval -15.22 to 10.56
|
-7.23 percentage change in LDL-C
Interval -18.56 to 4.36
|
|
Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C)
26 weeks (n=233, 231, 221)
|
-6.86 percentage change in LDL-C
Interval -18.26 to 8.2
|
-2.70 percentage change in LDL-C
Interval -15.33 to 9.15
|
-8.97 percentage change in LDL-C
Interval -20.21 to 5.0
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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
Percentage changes in triglycerides were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Outcome measures
| Measure |
1.5 mg LY2189265
n=266 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=265 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=265 Participants
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
|
|---|---|---|---|
|
Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides
26 weeks (n=252, 252, 253)
|
-2.35 percentage change in triglycerides
Interval -22.32 to 13.61
|
-1.96 percentage change in triglycerides
Interval -21.66 to 22.63
|
2.56 percentage change in triglycerides
Interval -16.0 to 23.79
|
|
Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides
52 weeks (n=255, 256, 254)
|
-4.27 percentage change in triglycerides
Interval -22.91 to 19.23
|
-0.86 percentage change in triglycerides
Interval -22.31 to 25.37
|
1.91 percentage change in triglycerides
Interval -21.65 to 24.04
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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.
Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured.
Outcome measures
| Measure |
1.5 mg LY2189265
n=266 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=267 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=267 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes
Amylase (total), 26 weeks
|
7.00 units per liter (U/L)
Interval 2.0 to 13.0
|
6.00 units per liter (U/L)
Interval 0.0 to 13.0
|
4.00 units per liter (U/L)
Interval -2.0 to 10.0
|
|
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes
Amylase (total), 52 weeks
|
5.50 units per liter (U/L)
Interval -1.0 to 13.0
|
5.00 units per liter (U/L)
Interval -1.0 to 13.0
|
4.00 units per liter (U/L)
Interval -2.0 to 9.0
|
|
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes
Amylase (PD), 26 weeks
|
5.00 units per liter (U/L)
Interval 2.0 to 9.0
|
4.00 units per liter (U/L)
Interval 1.0 to 7.0
|
1.00 units per liter (U/L)
Interval -1.0 to 5.0
|
|
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes
Amylase (PD), 52 weeks
|
4.00 units per liter (U/L)
Interval 1.0 to 7.0
|
3.00 units per liter (U/L)
Interval 0.0 to 8.0
|
2.00 units per liter (U/L)
Interval -1.0 to 5.0
|
|
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes
Lipase, 26 weeks
|
7.00 units per liter (U/L)
Interval 1.0 to 16.0
|
5.00 units per liter (U/L)
Interval 0.0 to 13.0
|
1.00 units per liter (U/L)
Interval -4.0 to 8.0
|
|
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes
Lipase, 52 weeks
|
5.00 units per liter (U/L)
Interval -1.0 to 13.0
|
5.00 units per liter (U/L)
Interval 0.0 to 12.0
|
1.00 units per liter (U/L)
Interval -4.0 to 6.0
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, and 52 weeksPopulation: 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
Outcome measures
| Measure |
1.5 mg LY2189265
n=266 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=267 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=267 Participants
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
|
|---|---|---|---|
|
Change From Baseline to 26 and 52 Weeks in Serum Calcitonin
26 weeks
|
0.00 picograms per milliliter (pcg/mL)
Interval 0.0 to 0.0
|
0.00 picograms per milliliter (pcg/mL)
Interval 0.0 to 0.0
|
0.00 picograms per milliliter (pcg/mL)
Interval 0.0 to 0.0
|
|
Change From Baseline to 26 and 52 Weeks in Serum Calcitonin
52 weeks
|
0.00 picograms per milliliter (pcg/mL)
Interval 0.0 to 0.0
|
0.00 picograms per milliliter (pcg/mL)
Interval 0.0 to 0.0
|
0.00 picograms per milliliter (pcg/mL)
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline through 52 weeksPopulation: Participants who received at least one dose of LY2189265 with evaluable LY2189265 ADA data.
A participant was considered to have treatment emergent LY2189265 anti-drug antibodies (ADA) if the participant had at least one titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. The total number of treatment emergent ADA was not analyzed at 26 weeks.
Outcome measures
| Measure |
1.5 mg LY2189265
n=521 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
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
|
|---|---|---|---|
|
Number of Participants With Treatment Emergent Anti-LY2189265 Antibodies
|
10 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 26 weeks and 52 weeksPopulation: Participants who received at least one dose of LY2189265 or Metformin. Only pre-rescue measurements were used.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
|
|---|---|---|---|
|
Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks
Severe, 26 weeks (n=241, 248, 236)
|
0 events
|
0 events
|
0 events
|
|
Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks
Severe, 52 weeks (n=214, 217, 199)
|
0 events
|
0 events
|
0 events
|
|
Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks
Documented Symptomatic, 26 weeks (n=241, 248, 236)
|
2 events
|
6 events
|
2 events
|
|
Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks
Documented Symptomatic, 52 weeks (n=214, 217, 199)
|
7 events
|
8 events
|
2 events
|
|
Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks
Asymptomatic, 26 weeks (n=241, 248, 236)
|
19 events
|
9 events
|
13 events
|
|
Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks
Asymptomatic, 52 weeks (n=214, 217, 199)
|
5 events
|
9 events
|
9 events
|
SECONDARY outcome
Timeframe: Baseline through 52 weeksPopulation: Participants who received at least one dose of LY2189265 or Metformin. Only pre-rescue measurements were used.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
|
|---|---|---|---|
|
Rate of Self-reported Hypoglycemic Events at 52 Weeks
Severe
|
0.00 events per participant per year
Standard Deviation 0.00
|
0.00 events per participant per year
Standard Deviation 0.00
|
0.00 events per participant per year
Standard Deviation 0.00
|
|
Rate of Self-reported Hypoglycemic Events at 52 Weeks
Documented Symptomatic
|
0.62 events per participant per year
Standard Deviation 8.91
|
0.15 events per participant per year
Standard Deviation 0.72
|
0.09 events per participant per year
Standard Deviation 0.50
|
|
Rate of Self-reported Hypoglycemic Events at 52 Weeks
Asymptomatic
|
0.24 events per participant per year
Standard Deviation 1.26
|
0.30 events per participant per year
Standard Deviation 1.85
|
0.18 events per participant per year
Standard Deviation 0.79
|
SECONDARY outcome
Timeframe: Baseline through 52 weeks plus 30-day follow upPopulation: Participants who received at least one dose of LY2189265 or Metformin. Only pre-rescue measurements were used.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
|
|---|---|---|---|
|
Number of Participants With Adjudicated Pancreatitis at 52 Weeks Plus 30-day Follow up
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline through 52 weeks plus 30-day follow upPopulation: Participants who received at least one dose of LY2189265 or Metformin.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=269 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 Participants
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
|
|---|---|---|---|
|
Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up
Any Nonfatal CV Event
|
1 participants
|
2 participants
|
1 participants
|
|
Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up
Any CV Event
|
1 participants
|
2 participants
|
1 participants
|
|
Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up
Any Fatal CV Event
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 4 weeks, 13 weeks, 26 weeks, and 52 weeksPopulation: Participants who received at least one dose of LY2189265 with evaluable LY2189265 concentration data.
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.
Outcome measures
| Measure |
1.5 mg LY2189265
n=144 Participants
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=146 Participants
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
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
|
|---|---|---|---|
|
Measurement of LY2189265 Drug Concentration for Pharmacokinetics: Area Under the Concentration Curve (AUC)
|
12036 nanogram hours per milliliter (ng*hr/mL)
Standard Deviation 5385
|
5919 nanogram hours per milliliter (ng*hr/mL)
Standard Deviation 1548
|
—
|
Adverse Events
1.5 mg LY2189265
0.75 mg LY2189265
Metformin
Serious adverse events
| Measure |
1.5 mg LY2189265
n=269 participants at risk
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 participants at risk
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 participants at risk
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
|
|---|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Cardiac disorders
Cardiac failure
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 2
|
|
Cardiac disorders
Coronary artery stenosis
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Gastrointestinal disorders
Diarrhoea haemorrhagic
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Gastrointestinal disorders
Oesophageal spasm
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
General disorders
Chest pain
|
0.00%
0/269
|
1.1%
3/270 • Number of events 3
|
0.00%
0/268
|
|
General disorders
Paradoxical drug reaction
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Hepatobiliary disorders
Gallbladder disorder
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Infections and infestations
Abdominal abscess
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Infections and infestations
Appendicitis
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Infections and infestations
Cellulitis
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Infections and infestations
Cholecystitis infective
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Infections and infestations
Disseminated tuberculosis
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Infections and infestations
Echinococciasis
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Infections and infestations
Gastroenteritis
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Infections and infestations
Hepatic echinococciasis
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Infections and infestations
Pharyngeal abscess
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Infections and infestations
Urinary tract infection
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.37%
1/269 • Number of events 1
|
0.74%
2/270 • Number of events 2
|
0.00%
0/268
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-hodgkin's lymphoma
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian fibroma
|
0.00%
0/155
|
0.00%
0/152
|
0.68%
1/147 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tongue carcinoma stage I
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Nervous system disorders
Convulsion
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Nervous system disorders
Presyncope
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
|
Nervous system disorders
Syncope
|
0.00%
0/269
|
0.74%
2/270 • Number of events 2
|
0.00%
0/268
|
|
Nervous system disorders
Transient ischaemic attack
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Nervous system disorders
VIth nerve paralysis
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.65%
1/155 • Number of events 1
|
0.00%
0/152
|
0.00%
0/147
|
|
Psychiatric disorders
Bipolar II disorder
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 2
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/269
|
0.37%
1/270 • Number of events 1
|
0.00%
0/268
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal turbinate hypertrophy
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/269
|
0.00%
0/270
|
0.37%
1/268 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.37%
1/269 • Number of events 1
|
0.00%
0/270
|
0.00%
0/268
|
Other adverse events
| Measure |
1.5 mg LY2189265
n=269 participants at risk
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
0.75 mg LY2189265
n=270 participants at risk
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks
|
Metformin
n=268 participants at risk
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
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
4.8%
13/269 • Number of events 18
|
4.8%
13/270 • Number of events 19
|
3.7%
10/268 • Number of events 14
|
|
Gastrointestinal disorders
Abdominal pain
|
4.1%
11/269 • Number of events 16
|
3.7%
10/270 • Number of events 11
|
2.2%
6/268 • Number of events 7
|
|
Gastrointestinal disorders
Constipation
|
6.7%
18/269 • Number of events 23
|
4.4%
12/270 • Number of events 13
|
1.1%
3/268 • Number of events 3
|
|
Gastrointestinal disorders
Diarrhoea
|
11.5%
31/269 • Number of events 37
|
9.6%
26/270 • Number of events 30
|
14.6%
39/268 • Number of events 44
|
|
Gastrointestinal disorders
Dyspepsia
|
4.5%
12/269 • Number of events 15
|
3.0%
8/270 • Number of events 22
|
2.2%
6/268 • Number of events 7
|
|
Gastrointestinal disorders
Nausea
|
19.7%
53/269 • Number of events 76
|
11.5%
31/270 • Number of events 45
|
16.0%
43/268 • Number of events 50
|
|
Gastrointestinal disorders
Vomiting
|
9.7%
26/269 • Number of events 32
|
7.4%
20/270 • Number of events 24
|
5.2%
14/268 • Number of events 70
|
|
Infections and infestations
Bronchitis
|
2.6%
7/269 • Number of events 8
|
4.1%
11/270 • Number of events 11
|
3.4%
9/268 • Number of events 9
|
|
Infections and infestations
Influenza
|
3.3%
9/269 • Number of events 11
|
4.1%
11/270 • Number of events 14
|
3.0%
8/268 • Number of events 13
|
|
Infections and infestations
Nasopharyngitis
|
5.2%
14/269 • Number of events 16
|
3.3%
9/270 • Number of events 10
|
10.4%
28/268 • Number of events 39
|
|
Infections and infestations
Upper respiratory tract infection
|
5.9%
16/269 • Number of events 16
|
6.3%
17/270 • Number of events 20
|
3.0%
8/268 • Number of events 10
|
|
Infections and infestations
Urinary tract infection
|
3.7%
10/269 • Number of events 11
|
4.1%
11/270 • Number of events 13
|
2.2%
6/268 • Number of events 7
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.7%
18/269 • Number of events 22
|
4.4%
12/270 • Number of events 15
|
4.5%
12/268 • Number of events 14
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.9%
5/269 • Number of events 5
|
3.3%
9/270 • Number of events 11
|
4.5%
12/268 • Number of events 13
|
|
Nervous system disorders
Dizziness
|
1.9%
5/269 • Number of events 6
|
4.4%
12/270 • Number of events 13
|
3.4%
9/268 • Number of events 12
|
|
Nervous system disorders
Headache
|
3.7%
10/269 • Number of events 14
|
5.2%
14/270 • Number of events 57
|
7.5%
20/268 • Number of events 28
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60