Trial Outcomes & Findings for A Study in Participants With Type 2 Diabetes Mellitus (NCT NCT01064687)

Last Updated: 2015-01-26

Results Overview

Least squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

978 participants

Primary outcome timeframe

Baseline, 26 weeks

Results posted on

2015-01-26

Participant Flow

Due to ethical considerations and to preserve the blinding of the study, participants randomized to placebo at baseline were reassigned at 26 weeks to either 1.5 mg LY2189265 or 0.75 mg LY2189265 from 26 weeks through 52 weeks.

Participant milestones

Participant milestones
Measure	1.5 mg LY2189265 LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks
Overall Study STARTED	279	280	278	141
Overall Study Received at Least 1 Dose of Study Drug	279	280	276	141
Overall Study Completed 26 Weeks	260	263	252	124
Overall Study COMPLETED	245	254	237	124
Overall Study NOT COMPLETED	34	26	41	17

Reasons for withdrawal

Reasons for withdrawal
Measure	1.5 mg LY2189265 LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks
Overall Study Adverse Event	9	4	10	3
Overall Study Death	1	1	0	0
Overall Study Entry Criteria Not Met	3	0	0	0
Overall Study Lack of Efficacy	1	0	2	3
Overall Study Lost to Follow-up	7	10	13	5
Overall Study Physician Decision	2	2	0	0
Overall Study Protocol Violation	1	1	0	1
Overall Study Sponsor Decision	0	0	3	0
Overall Study Withdrawal by Subject	9	7	12	5
Overall Study Treatment Noncompliance	1	1	1	0

Baseline Characteristics

A Study in Participants With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Total n=976 Participants Total of all reporting groups
Age, Continuous	56.25 years STANDARD_DEVIATION 9.72 • n=5 Participants	55.79 years STANDARD_DEVIATION 9.45 • n=7 Participants	55.45 years STANDARD_DEVIATION 10.15 • n=5 Participants	54.56 years STANDARD_DEVIATION 10.01 • n=4 Participants	55.65 years STANDARD_DEVIATION 9.81 • n=21 Participants
Sex: Female, Male Female	116 Participants n=5 Participants	112 Participants n=7 Participants	120 Participants n=5 Participants	58 Participants n=4 Participants	406 Participants n=21 Participants
Sex: Female, Male Male	163 Participants n=5 Participants	168 Participants n=7 Participants	156 Participants n=5 Participants	83 Participants n=4 Participants	570 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	93 Participants n=5 Participants	102 Participants n=7 Participants	91 Participants n=5 Participants	45 Participants n=4 Participants	331 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	186 Participants n=5 Participants	178 Participants n=7 Participants	184 Participants n=5 Participants	96 Participants n=4 Participants	644 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	40 Participants n=5 Participants	37 Participants n=7 Participants	38 Participants n=5 Participants	20 Participants n=4 Participants	135 Participants n=21 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	8 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants	24 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Black or African American	24 Participants n=5 Participants	24 Participants n=7 Participants	18 Participants n=5 Participants	10 Participants n=4 Participants	76 Participants n=21 Participants
Race (NIH/OMB) White	205 Participants n=5 Participants	207 Participants n=7 Participants	211 Participants n=5 Participants	103 Participants n=4 Participants	726 Participants n=21 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	11 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	226 participants n=5 Participants	226 participants n=7 Participants	223 participants n=5 Participants	113 participants n=4 Participants	788 participants n=21 Participants
Region of Enrollment Mexico	37 participants n=5 Participants	36 participants n=7 Participants	35 participants n=5 Participants	19 participants n=4 Participants	127 participants n=21 Participants
Region of Enrollment Argentina	16 participants n=5 Participants	18 participants n=7 Participants	18 participants n=5 Participants	9 participants n=4 Participants	61 participants n=21 Participants
Body Weight	96.22 kilograms STANDARD_DEVIATION 19.63 • n=5 Participants	95.53 kilograms STANDARD_DEVIATION 20.56 • n=7 Participants	97.37 kilograms STANDARD_DEVIATION 18.87 • n=5 Participants	94.12 kilograms STANDARD_DEVIATION 19.28 • n=4 Participants	96.04 kilograms STANDARD_DEVIATION 19.64 • n=21 Participants
Body Mass Index (BMI)	33.09 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 5.33 • n=5 Participants	33.00 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 5.50 • n=7 Participants	33.54 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 5.36 • n=5 Participants	32.90 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 5.66 • n=4 Participants	33.16 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 5.43 • n=21 Participants
Glycosylated Hemoglobin (HbA1c)	8.10 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.34 • n=5 Participants	8.05 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.24 • n=7 Participants	8.07 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.34 • n=5 Participants	8.06 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.31 • n=4 Participants	8.07 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.31 • n=21 Participants
Duration of Diabetes	8.76 years STANDARD_DEVIATION 5.59 • n=5 Participants	8.78 years STANDARD_DEVIATION 5.47 • n=7 Participants	8.84 years STANDARD_DEVIATION 5.71 • n=5 Participants	8.60 years STANDARD_DEVIATION 5.78 • n=4 Participants	8.76 years STANDARD_DEVIATION 5.61 • n=21 Participants
Fasting Serum Glucose	9.00 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.09 • n=5 Participants	8.84 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.76 • n=7 Participants	9.11 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.04 • n=5 Participants	9.22 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.01 • n=4 Participants	9.02 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.97 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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 and treatment as fixed effects and baseline HbA1c as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=271 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=269 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=266 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=119 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)	-1.51 percentage of glycosylated hemoglobin Standard Error 0.06	-1.30 percentage of glycosylated hemoglobin Standard Error 0.06	-0.99 percentage of glycosylated hemoglobin Standard Error 0.06	-0.46 percentage of glycosylated hemoglobin Standard Error 0.08	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable HbA1c data. Only pre-rescue measurements were used. 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 and treatment as fixed effects and baseline HbA1c as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=271 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=269 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=266 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)	-1.36 percentage of glycosylated hemoglobin Standard Error 0.08	-1.07 percentage of glycosylated hemoglobin Standard Error 0.08	-0.80 percentage of glycosylated hemoglobin Standard Error 0.08	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable body weight 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) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=259 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=253 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=245 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=109 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks for Body Weight	-1.34 kilograms (kg) Standard Error 0.25	0.18 kilograms (kg) Standard Error 0.25	-1.14 kilograms (kg) Standard Error 0.26	1.37 kilograms (kg) Standard Error 0.37	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable body weight data. Only pre-rescue measurements were used.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=238 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=231 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=210 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks for Body Weight	-1.08 kilograms (kg) Standard Error 0.34	0.49 kilograms (kg) Standard Error 0.34	-0.76 kilograms (kg) Standard Error 0.35	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable BMI 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, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=259 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=253 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=245 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=109 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks on Body Mass Index (BMI)	-0.48 kilograms per meter squared (kg/m^2) Standard Error 0.09	0.07 kilograms per meter squared (kg/m^2) Standard Error 0.09	-0.41 kilograms per meter squared (kg/m^2) Standard Error 0.09	0.49 kilograms per meter squared (kg/m^2) Standard Error 0.13	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable BMI data. Only pre-rescue measurements were used.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=238 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=231 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=210 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks on Body Mass Index (BMI)	-0.37 kilograms per meter squared (kg/m^2) Standard Error 0.12	0.18 kilograms per meter squared (kg/m^2) Standard Error 0.12	-0.28 kilograms per meter squared (kg/m^2) Standard Error 0.12	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable SMPG data. Only pre-rescue measurements were used.

The SMPG 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 a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=207 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=195 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=202 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=78 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles	-46.82 milligrams per deciliter (mg/dL) Standard Error 1.81	-42.09 milligrams per deciliter (mg/dL) Standard Error 1.87	-37.48 milligrams per deciliter (mg/dL) Standard Error 1.83	-18.07 milligrams per deciliter (mg/dL) Standard Error 2.68	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable SMPG data. Only pre-rescue measurements were used.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=187 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=185 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=178 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles	-43.84 milligrams per deciliter (mg/dL) Standard Error 2.07	-40.62 milligrams per deciliter (mg/dL) Standard Error 2.12	-36.16 milligrams per deciliter (mg/dL) Standard Error 2.11	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

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, country, and treatment as factors included in the model.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=271 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=269 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=266 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=119 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 26 Weeks HbA1c Less Than 7%	78.2 percentage of participants	65.8 percentage of participants	52.3 percentage of participants	42.9 percentage of participants	—
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 26 Weeks HbA1c Less Than or Equal to 6.5%	62.7 percentage of participants	53.2 percentage of participants	38.0 percentage of participants	24.4 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=271 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=269 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=266 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 52 Weeks HbA1c Less Than 7.0%	70.8 percentage of participants	59.1 percentage of participants	49.2 percentage of participants	—	—
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 52 Weeks HbA1c Less Than or Equal to 6.5%	57.2 percentage of participants	48.3 percentage of participants	34.6 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=238 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=218 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=223 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=98 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) HOMA2-%B	36.14 percentage of HOMA2 Standard Error 2.60	23.61 percentage of HOMA2 Standard Error 2.67	15.02 percentage of HOMA2 Standard Error 2.62	0.93 percentage of HOMA2 Standard Error 3.66	—
Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) HOMA2-%S	-3.14 percentage of HOMA2 Standard Error 2.91	1.16 percentage of HOMA2 Standard Error 2.97	-1.59 percentage of HOMA2 Standard Error 2.92	2.56 percentage of HOMA2 Standard Error 4.07	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable HOMA2-%B or HOMA2-%S data. Only pre-rescue measurements were used.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=219 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=202 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=187 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) HOMA2-%B	35.21 percentage of HOMA2 Standard Error 2.63	25.69 percentage of HOMA2 Standard Error 2.70	13.57 percentage of HOMA2 Standard Error 2.75	—	—
Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) HOMA2-%S	-7.48 percentage of HOMA2 Standard Error 2.93	-5.49 percentage of HOMA2 Standard Error 3.01	-3.75 percentage of HOMA2 Standard Error 3.07	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable EQ-5D 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 European Quality of Life - 5 dimensions (EQ-5D) questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part of the questionnaire consists of a visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) and adjusted by treatment, country, and baseline.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks in the EuroQol 5 VAS Health State Score (n=270, 267, 264, 119)	4.50 units on a scale Standard Error 0.85	2.41 units on a scale Standard Error 0.85	3.94 units on a scale Standard Error 0.85	0.71 units on a scale Standard Error 1.15	—
Change From Baseline to 26 Weeks in the EuroQol 5 EQ-5D UK (n=270, 266, 264, 119)	0.01 units on a scale Standard Error 0.01	0.01 units on a scale Standard Error 0.01	0.00 units on a scale Standard Error 0.01	-0.00 units on a scale Standard Error 0.02	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable EQ-5D data. Only pre-rescue measurements were used. 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

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks in the EuroQol 5 VAS Health State Score (n=270, 267, 264)	5.15 units on a scale Standard Error 0.89	3.52 units on a scale Standard Error 0.89	3.51 units on a scale Standard Error 0.89	—	—
Change From Baseline to 52 Weeks in the EuroQol 5 EQ-5D UK (n=270, 266, 264)	0.02 units on a scale Standard Error 0.01	0.01 units on a scale Standard Error 0.01	-0.00 units on a scale Standard Error 0.01	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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). The DTSQ change version (DTSQc) was not collected at 26 weeks. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline score as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=270 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=268 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=266 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=119 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Version	2.40 units on a scale Standard Error 0.34	2.56 units on a scale Standard Error 0.33	0.85 units on a scale Standard Error 0.33	0.49 units on a scale Standard Error 0.45	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable DTSQs or DTSQc data. Only pre-rescue measurements were used. 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 Treatment Satisfaction Questionnaire status (DTSQs) and change (DTSQc) versions are used to assess participant treatment satisfaction at each study visit and relative change in satisfaction from baseline, respectively. Both questionnaires consist 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 change version has the same 8 items as the status version with a small alteration of the wording of Item 7. 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) for the DTSQs and from -18 (much less satisfied) to +18 (much more satisfied) for the DTSQc. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline score as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions DTSQs Treatment Satisfaction (n=270, 268, 266)	2.05 units on a scale Standard Error 0.36	2.11 units on a scale Standard Error 0.36	0.69 units on a scale Standard Error 0.36	—	—
Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions DTSQc Treatment Satisfaction (n=249, 237, 226)	15.36 units on a scale Standard Error 0.40	15.46 units on a scale Standard Error 0.41	14.01 units on a scale Standard Error 0.41	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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) with country and treatment as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=270 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=267 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=266 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=119 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks in the Impact of Weight on Activities of Daily Living	0.18 units on a scale Standard Error 0.27	0.12 units on a scale Standard Error 0.27	0.47 units on a scale Standard Error 0.27	0.03 units on a scale Standard Error 0.36	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable APPADL data. Only pre-rescue measurements were used. 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

Outcome measures
Measure	1.5 mg LY2189265 n=270 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=267 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=266 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks in the Impact of Weight on Activities of Daily Living	0.18 units on a scale Standard Error 0.29	-0.18 units on a scale Standard Error 0.29	0.35 units on a scale Standard Error 0.29	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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) with country and treatment as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=270 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=267 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=266 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=119 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks on the Impact of Weight on Self-Perception	0.56 units on a scale Standard Error 0.15	0.47 units on a scale Standard Error 0.15	0.46 units on a scale Standard Error 0.15	0.45 units on a scale Standard Error 0.20	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable IW-SP data. Only pre-rescue measurements were used. 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

Outcome measures
Measure	1.5 mg LY2189265 n=270 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=267 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=266 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks on the Impact of Weight on Self-Perception	0.50 units on a scale Standard Error 0.15	0.47 units on a scale Standard Error 0.15	0.64 units on a scale Standard Error 0.15	—	—

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug. The number of participants with adjudicated CV events was not collected at 26 weeks.

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. At prespecified visits, participants were asked about any new CV event since the previous inquiry. 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. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Any CV Event	3 participants	2 participants	2 participants	—	—
Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Any Fatal Event	1 participants	0 participants	0 participants	—	—
Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Any Non-fatal CV Event	3 participants	2 participants	2 participants	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval QTcF Interval (n=253, 260, 250, 120)	-1.11 milliseconds (msec) Standard Error 1.00	0.91 milliseconds (msec) Standard Error 0.99	1.21 milliseconds (msec) Standard Error 1.00	1.32 milliseconds (msec) Standard Error 1.33	—
Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval PR Interval (n=252, 259, 246, 116)	2.35 milliseconds (msec) Standard Error 0.89	0.93 milliseconds (msec) Standard Error 0.88	1.01 milliseconds (msec) Standard Error 0.89	-1.83 milliseconds (msec) Standard Error 1.20	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable ECG QTcF Interval or PR Interval data.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval QTcF Interval (n=239, 243, 226)	1.28 milliseconds (msec) Standard Error 1.07	2.30 milliseconds (msec) Standard Error 1.07	2.52 milliseconds (msec) Standard Error 1.10	—	—
Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval PR Interval (n=237, 243, 220)	2.57 milliseconds (msec) Standard Error 0.96	0.69 milliseconds (msec) Standard Error 0.96	-0.82 milliseconds (msec) Standard Error 0.99	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable seated pulse rate data.

Seated 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, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=263 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=266 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=259 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=127 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change in Baseline to 26 Weeks on Pulse Rate	2.80 beats per minute (bpm) Standard Error 0.52	2.80 beats per minute (bpm) Standard Error 0.51	1.18 beats per minute (bpm) Standard Error 0.52	0.61 beats per minute (bpm) Standard Error 0.70	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable seated pulse rate data.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=248 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=256 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=238 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change in Baseline to 52 Weeks on Pulse Rate	1.68 beats per minute (bpm) Standard Error 0.56	1.56 beats per minute (bpm) Standard Error 0.55	1.15 beats per minute (bpm) Standard Error 0.56	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least one dose of LY2189265, Exenatide, or Placebo with evaluable blood pressure data.

Seated systolic blood pressure (SBP) and seated 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, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks on Blood Pressure Seated SBP (n=263, 266, 259, 127)	0.11 millimeters of mercury (mmHg) Standard Error 0.83	-0.36 millimeters of mercury (mmHg) Standard Error 0.82	0.06 millimeters of mercury (mmHg) Standard Error 0.83	3.40 millimeters of mercury (mmHg) Standard Error 1.13	—
Change From Baseline to 26 Weeks on Blood Pressure Seated DBP (n=263, 266, 259, 127)	0.76 millimeters of mercury (mmHg) Standard Error 0.55	0.56 millimeters of mercury (mmHg) Standard Error 0.54	-0.11 millimeters of mercury (mmHg) Standard Error 0.55	1.25 millimeters of mercury (mmHg) Standard Error 0.75	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable blood pressure data.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks on Blood Pressure Seated SBP (n=248, 256, 238)	0.83 millimeters of mercury (mmHg) Standard Error 0.87	1.62 millimeters of mercury (mmHg) Standard Error 0.85	0.02 millimeters of mercury (mmHg) Standard Error 0.88	—	—
Change From Baseline to 52 Weeks on Blood Pressure Seated DBP (n=248, 256, 238)	0.89 millimeters of mercury (mmHg) Standard Error 0.57	0.76 millimeters of mercury (mmHg) Standard Error 0.57	0.02 millimeters of mercury (mmHg) Standard Error 0.58	—	—

SECONDARY outcome

Timeframe: Baseline through 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo.

The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Participants With Adjudicated Pancreatitis at 26 Weeks	0 participants	0 participants	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: Participants who were randomized at baseline to LY2189265, Exenatide, or Placebo and received at least 1 dose of study drug.

The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 52 weeks, with the exception of the Placebo/1.5 mg LY2189265 and Placebo/0.75 mg LY2189265 treatment groups, which include only participants with confirmed pancreatitis during treatment with LY2189265 (26 weeks through 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

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=62 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 n=62 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Participants With Adjudicated Pancreatitis at 52 Weeks	1 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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) and lipase concentrations were measured.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks on Pancreatic Enzymes Amylase, Total (n=253, 253, 254, 127)	12.50 units per liter Inter-Quartile Range 26.55 • Interval -3.57 to 28.85	3.28 units per liter Inter-Quartile Range 24.24 • Interval -9.88 to 20.0	5.56 units per liter Inter-Quartile Range 26.61 • Interval -9.52 to 18.46	-3.33 units per liter Inter-Quartile Range 27.51 • Interval -15.79 to 11.36	—
Change From Baseline to 26 Weeks on Pancreatic Enzymes Amylase, Pancreas-derived (n=237, 247, 246, 122)	14.81 units per liter Interval 0.0 to 35.0	10.34 units per liter Interval -5.88 to 26.67	5.56 units per liter Interval -7.14 to 21.05	-3.77 units per liter Interval -13.33 to 13.64	—
Change From Baseline to 26 Weeks on Pancreatic Enzymes Lipase (n=198, 203, 222, 114)	10.34 units per liter Interval -7.5 to 29.41	0.00 units per liter Interval -15.91 to 23.08	3.94 units per liter Interval -10.26 to 23.08	-9.53 units per liter Interval -23.33 to 6.67	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug 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) and lipase concentrations were measured.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks on Pancreatic Enzymes Amylase, Total (n=255, 263, 261)	9.21 units per liter Interval -4.95 to 23.19	2.78 units per liter Interval -11.67 to 17.5	2.38 units per liter Interval -11.86 to 15.22	—	—
Change From Baseline to 52 Weeks on Pancreatic Enzymes Amylase, Pancreas-derived (n=236, 253, 246)	16.67 units per liter Interval 0.0 to 35.6	7.69 units per liter Interval -8.7 to 28.0	7.85 units per liter Interval -8.82 to 26.67	—	—
Change From Baseline to 52 Weeks on Pancreatic Enzymes Lipase (n=201, 205, 221)	5.45 units per liter Interval -7.69 to 26.92	0.00 units per liter Interval -18.18 to 15.63	3.57 units per liter Interval -13.95 to 22.58	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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

Outcome measures
Measure	1.5 mg LY2189265 n=275 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=277 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=272 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=139 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks on Serum Calcitonin	0.20 picograms per milliliter (pg/mL) Standard Deviation 1.20	0.22 picograms per milliliter (pg/mL) Standard Deviation 1.91	0.05 picograms per milliliter (pg/mL) Standard Deviation 1.48	0.05 picograms per milliliter (pg/mL) Standard Deviation 0.89	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug 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

Outcome measures
Measure	1.5 mg LY2189265 n=275 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=277 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=272 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks on Serum Calcitonin	0.21 picograms per milliliter (pg/mL) Standard Deviation 1.29	0.05 picograms per milliliter (pg/mL) Standard Deviation 1.79	0.10 picograms per milliliter (pg/mL) Standard Deviation 1.67	—	—

SECONDARY outcome

Timeframe: Baseline through 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo.

Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of less than or equal to 3.9 millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Self-reported Hypoglycemic Events at 26 Weeks Severe HE	0 events	0 events	1 events	0 events	—
Number of Self-reported Hypoglycemic Events at 26 Weeks Documented Symptomatic HE	31 events	25 events	146 events	4 events	—
Number of Self-reported Hypoglycemic Events at 26 Weeks Asymptomatic HE	26 events	95 events	51 events	5 events	—
Number of Self-reported Hypoglycemic Events at 26 Weeks Nocturnal HE	9 events	15 events	31 events	6 events	—
Number of Self-reported Hypoglycemic Events at 26 Weeks Probable Symptomatic HE	5 events	16 events	3 events	3 events	—

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug.

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

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Self-reported Hypoglycemic Events at 52 Weeks Severe HE	0 events	0 events	2 events	—	—
Number of Self-reported Hypoglycemic Events at 52 Weeks Documented Symptomatic HE	53 events	39 events	205 events	—	—
Number of Self-reported Hypoglycemic Events at 52 Weeks Asymptomatic HE	47 events	157 events	98 events	—	—
Number of Self-reported Hypoglycemic Events at 52 Weeks Nocturnal HE	20 events	29 events	57 events	—	—
Number of Self-reported Hypoglycemic Events at 52 Weeks Probable Symptomatic HE	8 events	22 events	4 events	—	—

SECONDARY outcome

Timeframe: Baseline through 26 weeks

Population: Participants who were randomized and received at least one dose of LY2189265, Exenatide, or Placebo. Only pre-rescue measurements were used.

Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of equal to or less than 3.9 millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of equal to or less than 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Rate of Self-reported Hypoglycemic Events at 26 Weeks Severe HE	0.00 events per participant per year Standard Deviation 0.00	0.00 events per participant per year Standard Deviation 0.00	0.01 events per participant per year Standard Deviation 0.12	0.00 events per participant per year Standard Deviation 0.00	—
Rate of Self-reported Hypoglycemic Events at 26 Weeks Documented symptomatic HE	0.22 events per participant per year Standard Deviation 1.94	0.18 events per participant per year Standard Deviation 0.97	1.07 events per participant per year Standard Deviation 4.90	0.06 events per participant per year Standard Deviation 0.48	—
Rate of Self-reported Hypoglycemic Events at 26 Weeks Asymptomatic HE	0.19 events per participant per year Standard Deviation 1.13	0.69 events per participant per year Standard Deviation 4.74	0.38 events per participant per year Standard Deviation 1.74	0.27 events per participant per year Standard Deviation 2.44	—
Rate of Self-reported Hypoglycemic Events at 26 Weeks Nocturnal HE	0.06 events per participant per year Standard Deviation 0.60	0.19 events per participant per year Standard Deviation 1.74	0.23 events per participant per year Standard Deviation 1.16	0.27 events per participant per year Standard Deviation 2.51	—
Rate of Self-reported Hypoglycemic Events at 26 Weeks Probable symptomatic HE	0.04 events per participant per year Standard Deviation 0.37	0.24 events per participant per year Standard Deviation 2.44	0.02 events per participant per year Standard Deviation 0.21	0.04 events per participant per year Standard Deviation 0.51	—

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug. Only pre-rescue measurements were used.

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

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Rate of Self-reported Hypoglycemic Events at 52 Weeks Severe HE	0.00 events per participant per year Standard Deviation 0.00	0.00 events per participant per year Standard Deviation 0.00	0.01 events per participant per year Standard Deviation 0.09	—	—
Rate of Self-reported Hypoglycemic Events at 52 Weeks Documented symptomatic HE	0.19 events per participant per year Standard Deviation 1.23	0.14 events per participant per year Standard Deviation 0.78	0.76 events per participant per year Standard Deviation 3.18	—	—
Rate of Self-reported Hypoglycemic Events at 52 Weeks Asymptomatic HE	0.17 events per participant per year Standard Deviation 1.05	0.56 events per participant per year Standard Deviation 3.57	0.37 events per participant per year Standard Deviation 1.81	—	—
Rate of Self-reported Hypoglycemic Events at 52 Weeks Nocturnal HE	0.07 events per participant per year Standard Deviation 0.63	0.19 events per participant per year Standard Deviation 1.72	0.21 events per participant per year Standard Deviation 1.06	—	—
Rate of Self-reported Hypoglycemic Events at 52 Weeks Probable symptomatic HE	0.03 events per participant per year Standard Deviation 0.26	0.21 events per participant per year Standard Deviation 2.38	0.02 events per participant per year Standard Deviation 0.16	—	—

SECONDARY outcome

Timeframe: Baseline through 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo.

Rescue therapy was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period. Time to start first new glucose-lowering intervention due to hyperglycemia ("rescue therapy") was analyzed between the groups using the semi-parametric proportional hazard regression model with treatment group and country as fixed effects and baseline glycosylated hemoglobin (HbA1c) as a covariate.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 26 Weeks	4 participants	14 participants	13 participants	22 participants	—

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 52 Weeks	10 participants	27 participants	31 participants	—	—

SECONDARY outcome

Timeframe: Baseline through 26 weeks

Population: Participants who were randomized and received at least one dose of LY2189265, Exenatide, or Placebo with evaluable LY2189265 ADA data. In the clinically evaluated dose range of LY2189265, no dose effect on the magnitude of the anti-LY2189265 immune response was observed. Therefore, results were combined for the 0.75 mg and 1.5 mg LY2189265 groups.

LY2189265 (Dulaglutide) anti-drug antibodies (ADA) were assessed. The number of participants with initial postbaseline detection of treatment emergent (defined as a 4-fold increase in the ADA titer from baseline) LY2189265 ADA were summarized.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=559 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=276 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=141 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Participants With LY2189265 Antibodies at 26 Weeks	6 participants	12 participants	2 participants	—	—

SECONDARY outcome

Timeframe: 26 weeks through 52 weeks and 53 weeks through 4 weeks after last dose

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=552 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=270 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=123 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug 52 weeks	3 participants	2 participants	2 participants	—	—
Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug 4 weeks after last study dose	1 participants	0 participants	1 participants	—	—

SECONDARY outcome

Timeframe: Baseline through 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo.

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 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Participants With Treatment Emergent Adverse Events at 26 Weeks	215 participants	199 participants	198 participants	104 participants	—

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: Participants who were randomized at baseline to LY2189265, Exenatide, or Placebo and received at least 1 dose of study drug.

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 52 weeks, with the exception of the Placebo/1.5 mg LY2189265 and Placebo/0.75 mg LY2189265 treatment groups, which include only TEAEs that occurred during treatment with LY2189265 (26 weeks through 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

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=62 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 n=62 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Number of Participants With Treatment Emergent Adverse Events at 52 Weeks	226 participants	220 participants	221 participants	47 participants	41 participants

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=141 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks in Hematological and Biochemical Lab Values	NA (LEAST_SQUARES_MEAN) Standard Error NA No clinically relevant changes from baseline to 26 weeks in hematological and biochemical laboratory values were noted, with the exception of pancreatic enzymes and calcitonin measures, which are reported in separate outcome measures.	NA (LEAST_SQUARES_MEAN) Standard Error NA No clinically relevant changes from baseline to 26 weeks in hematological and biochemical laboratory values were noted, with the exception of pancreatic enzymes and calcitonin measures, which are reported in separate outcome measures.	NA (LEAST_SQUARES_MEAN) Standard Error NA No clinically relevant changes from baseline to 26 weeks in hematological and biochemical laboratory values were noted, with the exception of pancreatic enzymes and calcitonin measures, which are reported in separate outcome measures.	NA (LEAST_SQUARES_MEAN) Standard Error NA No clinically relevant changes from baseline to 26 weeks in hematological and biochemical laboratory values were noted, with the exception of pancreatic enzymes and calcitonin measures, which are reported in separate outcome measures.	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	1.5 mg LY2189265 n=279 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=280 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=276 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 52 Weeks in Hematological and Biochemical Lab Values	NA (LEAST_SQUARES_MEAN) Standard Error NA No clinically relevant changes from baseline to 26 weeks in hematological and biochemical laboratory values were noted, with the exception of pancreatic enzymes and calcitonin measures, which are reported in separate outcome measures.	NA (LEAST_SQUARES_MEAN) Standard Error NA No clinically relevant changes from baseline to 26 weeks in hematological and biochemical laboratory values were noted, with the exception of pancreatic enzymes and calcitonin measures, which are reported in separate outcome measures.	NA (LEAST_SQUARES_MEAN) Standard Error NA No clinically relevant changes from baseline to 26 weeks in hematological and biochemical laboratory values were noted, with the exception of pancreatic enzymes and calcitonin measures, which are reported in separate outcome measures.	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable NT-proBNP 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

Outcome measures
Measure	1.5 mg LY2189265 n=255 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=254 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide n=246 Participants Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo n=119 Participants Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Change From Baseline to 26 Weeks in N Terminal Pro Brain Natriuretic Peptide (NT-proBNP)	-6.77 picograms per milliliter (pg/mL) Inter-Quartile Range 91.13 • Interval -30.45 to 15.22	-2.96 picograms per milliliter (pg/mL) Inter-Quartile Range 189.94 • Interval -22.83 to 19.45	-3.38 picograms per milliliter (pg/mL) Inter-Quartile Range 208.92 • Interval -31.29 to 18.61	-0.85 picograms per milliliter (pg/mL) Inter-Quartile Range 133.04 • Interval -25.37 to 17.76	—

SECONDARY outcome

Timeframe: 4 weeks, 13 weeks, 26 weeks, and 52 weeks

Population: Participants who were randomized at baseline to LY2189265 and received at least 1 dose of study drug with evaluable AUC 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

Outcome measures
Measure	1.5 mg LY2189265 n=325 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 n=321 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks Pioglitazone: at least 30 mg/day, oral, for 26 weeks	Placebo/0.75 mg LY2189265 Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks
Pharmacokinetics: Area Under the Concentration Curve (AUC) for LY2189265	12383 nanogram hours per milliliter (ng*hr/mL) Standard Deviation 5433	6627 nanogram hours per milliliter (ng*hr/mL) Standard Deviation 2487	—	—	—

Adverse Events

0.75 mg LY2189265 (Baseline Through 26 Weeks)

Serious events: 15 serious events

Other events: 194 other events

Deaths: 0 deaths

1.5 mg LY2189265 (Baseline Through 26 Weeks)

Serious events: 12 serious events

Other events: 215 other events

Deaths: 0 deaths

Exenatide (Baseline Through 26 Weeks)

Serious events: 15 serious events

Other events: 196 other events

Deaths: 0 deaths

Placebo (Baseline Through 26 Weeks)

Serious events: 12 serious events

Other events: 103 other events

Deaths: 0 deaths

0.75 mg LY2189265 (Baseline Through 56 Weeks)

Serious events: 22 serious events

Other events: 218 other events

Deaths: 0 deaths

1.5 mg LY2189265 (Baseline Through 56 Weeks)

Serious events: 18 serious events

Other events: 228 other events

Deaths: 0 deaths

Exenatide (Baseline Through 56 Weeks)

Serious events: 27 serious events

Other events: 223 other events

Deaths: 0 deaths

Placebo/0.75 mg LY2189265 (26 Weeks Through 56 Weeks)

Serious events: 6 serious events

Other events: 47 other events

Deaths: 0 deaths

Placebo/1.5 mg LY2189265 (26 Weeks Through 56 Weeks)

Serious events: 9 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	0.75 mg LY2189265 (Baseline Through 26 Weeks) n=280 participants at risk LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	1.5 mg LY2189265 (Baseline Through 26 Weeks) n=279 participants at risk LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide (Baseline Through 26 Weeks) n=278 participants at risk Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo (Baseline Through 26 Weeks) n=141 participants at risk Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): After 26 weeks, participants were randomized to receive either 0.75 milligrams (mg) or 1.5 mg, SC, once weekly for an additional 26 weeks (from week 26 through week 52) Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 (Baseline Through 56 Weeks) n=280 participants at risk LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	1.5 mg LY2189265 (Baseline Through 56 Weeks) n=279 participants at risk LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide (Baseline Through 56 Weeks) n=278 participants at risk Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo/0.75 mg LY2189265 (26 Weeks Through 56 Weeks) n=62 participants at risk Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks All events were treatment emergent during the LY2189265 treatment period.	Placebo/1.5 mg LY2189265 (26 Weeks Through 56 Weeks) n=62 participants at risk Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 1.5 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks All events were treatment emergent during the LY2189265 treatment period.
Nervous system disorders Convulsion	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Nervous system disorders Syncope	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Psychiatric disorders Delirium	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Nervous system disorders Peroneal nerve palsy	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Psychiatric disorders Impaired self-care	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Psychiatric disorders Major depression	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Psychiatric disorders Suicidal ideation	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/62	1.6% 1/62 • Number of events 1
Renal and urinary disorders Bladder perforation	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Renal and urinary disorders Nephrolithiasis	0.00% 0/280	0.36% 1/279 • Number of events 1	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Reproductive system and breast disorders Endometrial hyperplasia	0.00% 0/112	0.86% 1/116 • Number of events 1	0.00% 0/121	0.00% 0/58	0.00% 0/112	0.86% 1/116 • Number of events 1	0.00% 0/121	0.00% 0/26	0.00% 0/27
Blood and lymphatic system disorders Anaemia	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.00% 0/278	1.6% 1/62 • Number of events 1	0.00% 0/62
Cardiac disorders Acute myocardial infarction	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	1.6% 1/62 • Number of events 1	0.00% 0/62
Cardiac disorders Angina pectoris	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Cardiac disorders Atrial fibrillation	0.00% 0/280	0.72% 2/279 • Number of events 2	0.00% 0/278	1.4% 2/141 • Number of events 2	0.00% 0/280	0.72% 2/279 • Number of events 2	0.00% 0/278	1.6% 1/62 • Number of events 1	1.6% 1/62 • Number of events 1
Cardiac disorders Cardiac arrest	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Cardiac disorders Cardiac failure congestive	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.72% 2/279 • Number of events 2	0.00% 0/278	0.00% 0/62	0.00% 0/62
Cardiac disorders Coronary artery disease	0.36% 1/280 • Number of events 1	0.00% 0/279	0.36% 1/278 • Number of events 1	0.71% 1/141 • Number of events 1	0.36% 1/280 • Number of events 1	0.00% 0/279	0.36% 1/278 • Number of events 1	1.6% 1/62 • Number of events 1	0.00% 0/62
Cardiac disorders Myocardial infarction	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Cardiac disorders Myocardial ischaemia	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.71% 1/141 • Number of events 1	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/62	1.6% 1/62 • Number of events 1
Cardiac disorders Sinus bradycardia	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Cardiac disorders Supraventricular extrasystoles	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Cardiac disorders Ventricular fibrillation	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Endocrine disorders Hyperparathyroidism	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
Gastrointestinal disorders Colitis ulcerative	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Gastrointestinal disorders Gastric ulcer	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
Gastrointestinal disorders Gastritis	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Gastrointestinal disorders Gastrooesophageal sphincter insufficiency	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Gastrointestinal disorders Oesophagitis	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
Gastrointestinal disorders Pancreatitis acute	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Gastrointestinal disorders Umbilical hernia, obstructive	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/62	1.6% 1/62 • Number of events 1
General disorders Chest pain	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.71% 1/141 • Number of events 1	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/62	1.6% 1/62 • Number of events 1
General disorders Death	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
General disorders Gait disturbance	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
General disorders Non-cardiac chest pain	0.00% 0/280	0.36% 1/279 • Number of events 1	0.36% 1/278 • Number of events 1	0.00% 0/141	0.36% 1/280 • Number of events 1	0.36% 1/279 • Number of events 1	0.72% 2/278 • Number of events 2	0.00% 0/62	0.00% 0/62
General disorders Thrombosis in device	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Hepatobiliary disorders Biliary colic	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Hepatobiliary disorders Cholecystitis acute	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Hepatobiliary disorders Cholelithiasis	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.72% 2/279 • Number of events 2	0.00% 0/278	0.00% 0/62	0.00% 0/62
Infections and infestations Abscess	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.71% 1/141 • Number of events 1	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/62	1.6% 1/62 • Number of events 1
Infections and infestations Appendicitis	1.1% 3/280 • Number of events 3	0.00% 0/279	0.00% 0/278	0.00% 0/141	1.1% 3/280 • Number of events 3	0.36% 1/279 • Number of events 1	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Infections and infestations Bronchitis	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.71% 1/141 • Number of events 1	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Infections and infestations Cellulitis	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.71% 1/141 • Number of events 1	0.00% 0/280	0.72% 2/279 • Number of events 2	0.00% 0/278	1.6% 1/62 • Number of events 1	0.00% 0/62
Infections and infestations Gangrene	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Infections and infestations Gastroenteritis	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Infections and infestations Human anaplasmosis	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Infections and infestations Localised infection	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.71% 1/141 • Number of events 1	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/62	1.6% 1/62 • Number of events 1
Infections and infestations Osteomyelitis	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.71% 1/141 • Number of events 1	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	3.2% 2/62 • Number of events 2	0.00% 0/62
Infections and infestations Pelvic abscess	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Infections and infestations Pneumonia	0.71% 2/280 • Number of events 2	0.00% 0/279	0.00% 0/278	0.71% 1/141 • Number of events 1	0.71% 2/280 • Number of events 2	0.00% 0/279	0.00% 0/278	0.00% 0/62	1.6% 1/62 • Number of events 1
Infections and infestations Renal abscess	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Infections and infestations Sepsis syndrome	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Infections and infestations Staphylococcal infection	0.00% 0/280	0.00% 0/279	0.72% 2/278 • Number of events 2	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.72% 2/278 • Number of events 2	0.00% 0/62	0.00% 0/62
Infections and infestations Staphylococcal sepsis	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Infections and infestations Subcutaneous abscess	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.71% 2/280 • Number of events 2	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
Infections and infestations Urinary tract infection	0.00% 0/280	0.36% 1/279 • Number of events 1	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.72% 2/278 • Number of events 2	0.00% 0/62	0.00% 0/62
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Injury, poisoning and procedural complications Subdural haematoma	0.36% 1/280 • Number of events 1	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.71% 2/280 • Number of events 2	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Injury, poisoning and procedural complications Tendon injury	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.71% 1/141 • Number of events 1	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/62	1.6% 1/62 • Number of events 1
Injury, poisoning and procedural complications Wound complication	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Metabolism and nutrition disorders Dehydration	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.72% 2/278 • Number of events 2	1.6% 1/62 • Number of events 1	0.00% 0/62
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/280	0.36% 1/279 • Number of events 1	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Musculoskeletal and connective tissue disorders Neck pain	0.36% 1/280 • Number of events 1	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/280	0.00% 0/279	0.72% 2/278 • Number of events 2	0.00% 0/141	0.00% 0/280	0.00% 0/279	1.1% 3/278 • Number of events 3	0.00% 0/62	0.00% 0/62
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumour	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyoma	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Liposarcoma	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/168	0.00% 0/163	0.00% 0/157	1.2% 1/83 • Number of events 1	0.00% 0/168	0.00% 0/163	0.00% 0/157	0.00% 0/36	0.00% 0/35
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer stage 0	0.00% 0/168	0.00% 0/163	0.00% 0/157	0.00% 0/83	0.60% 1/168 • Number of events 1	0.00% 0/163	0.00% 0/157	0.00% 0/36	0.00% 0/35
Nervous system disorders Altered state of consciousness	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Nervous system disorders Cerebrovascular accident	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.36% 1/279 • Number of events 1	0.00% 0/278	0.00% 0/62	0.00% 0/62
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Respiratory, thoracic and mediastinal disorders Asthma	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.00% 0/278	1.6% 1/62 • Number of events 1	0.00% 0/62
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.00% 0/278	1.6% 1/62 • Number of events 1	0.00% 0/62
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.71% 1/141 • Number of events 1	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
Surgical and medical procedures Knee arthroplasty	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.36% 1/280 • Number of events 1	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
Surgical and medical procedures Rehabilitation therapy	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.36% 1/278 • Number of events 1	0.00% 0/62	0.00% 0/62
Vascular disorders Deep vein thrombosis	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.71% 1/141 • Number of events 1	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/62	0.00% 0/62
Vascular disorders Hypertensive crisis	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/141	0.00% 0/280	0.00% 0/279	0.00% 0/278	0.00% 0/62	1.6% 1/62 • Number of events 1

Other adverse events

Other adverse events
Measure	0.75 mg LY2189265 (Baseline Through 26 Weeks) n=280 participants at risk LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	1.5 mg LY2189265 (Baseline Through 26 Weeks) n=279 participants at risk LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide (Baseline Through 26 Weeks) n=278 participants at risk Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo (Baseline Through 26 Weeks) n=141 participants at risk Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): After 26 weeks, participants were randomized to receive either 0.75 milligrams (mg) or 1.5 mg, SC, once weekly for an additional 26 weeks (from week 26 through week 52) Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	0.75 mg LY2189265 (Baseline Through 56 Weeks) n=280 participants at risk LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	1.5 mg LY2189265 (Baseline Through 56 Weeks) n=279 participants at risk LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Exenatide (Baseline Through 56 Weeks) n=278 participants at risk Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks	Placebo/0.75 mg LY2189265 (26 Weeks Through 56 Weeks) n=62 participants at risk Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 0.75 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks All events were treatment emergent during the LY2189265 treatment period.	Placebo/1.5 mg LY2189265 (26 Weeks Through 56 Weeks) n=62 participants at risk Placebo: subcutaneous (SC), once weekly for 26 weeks LY2189265 (Dulaglutide): 1.5 milligrams (mg), SC, once weekly from week 26 through week 52 Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks Pioglitazone: at least 30 mg/day, oral, for 52 weeks All events were treatment emergent during the LY2189265 treatment period.
Gastrointestinal disorders Constipation	1.8% 5/280 • Number of events 6	4.3% 12/279 • Number of events 15	1.8% 5/278 • Number of events 6	1.4% 2/141 • Number of events 2	1.8% 5/280 • Number of events 6	5.7% 16/279 • Number of events 19	1.8% 5/278 • Number of events 6	3.2% 2/62 • Number of events 2	6.5% 4/62 • Number of events 6
Gastrointestinal disorders Diarrhoea	7.9% 22/280 • Number of events 42	11.1% 31/279 • Number of events 55	5.8% 16/278 • Number of events 22	5.7% 8/141 • Number of events 12	9.3% 26/280 • Number of events 47	13.3% 37/279 • Number of events 67	7.9% 22/278 • Number of events 38	8.1% 5/62 • Number of events 14	12.9% 8/62 • Number of events 8
Gastrointestinal disorders Dyspepsia	1.8% 5/280 • Number of events 6	7.9% 22/279 • Number of events 36	6.8% 19/278 • Number of events 19	2.8% 4/141 • Number of events 4	2.1% 6/280 • Number of events 7	8.2% 23/279 • Number of events 37	7.6% 21/278 • Number of events 21	0.00% 0/62	9.7% 6/62 • Number of events 9
Gastrointestinal disorders Flatulence	1.1% 3/280 • Number of events 4	5.0% 14/279 • Number of events 15	2.2% 6/278 • Number of events 7	2.1% 3/141 • Number of events 3	1.1% 3/280 • Number of events 4	5.7% 16/279 • Number of events 17	2.5% 7/278 • Number of events 8	0.00% 0/62	4.8% 3/62 • Number of events 4
Gastrointestinal disorders Nausea	16.1% 45/280 • Number of events 60	28.0% 78/279 • Number of events 108	25.5% 71/278 • Number of events 86	5.7% 8/141 • Number of events 8	16.8% 47/280 • Number of events 64	29.4% 82/279 • Number of events 114	27.7% 77/278 • Number of events 101	9.7% 6/62 • Number of events 6	24.2% 15/62 • Number of events 17
Gastrointestinal disorders Vomiting	6.1% 17/280 • Number of events 29	16.8% 47/279 • Number of events 67	10.8% 30/278 • Number of events 40	1.4% 2/141 • Number of events 2	6.1% 17/280 • Number of events 29	17.2% 48/279 • Number of events 68	12.2% 34/278 • Number of events 52	4.8% 3/62 • Number of events 5	8.1% 5/62 • Number of events 5
General disorders Fatigue	4.3% 12/280 • Number of events 16	3.6% 10/279 • Number of events 11	7.6% 21/278 • Number of events 21	1.4% 2/141 • Number of events 3	4.6% 13/280 • Number of events 17	4.7% 13/279 • Number of events 14	7.9% 22/278 • Number of events 23	4.8% 3/62 • Number of events 5	3.2% 2/62 • Number of events 2
General disorders Oedema peripheral	4.6% 13/280 • Number of events 13	1.1% 3/279 • Number of events 3	4.0% 11/278 • Number of events 12	5.0% 7/141 • Number of events 7	5.4% 15/280 • Number of events 16	2.9% 8/279 • Number of events 8	6.1% 17/278 • Number of events 18	14.5% 9/62 • Number of events 10	4.8% 3/62 • Number of events 3
Infections and infestations Influenza	2.9% 8/280 • Number of events 8	1.8% 5/279 • Number of events 5	2.5% 7/278 • Number of events 8	2.8% 4/141 • Number of events 4	4.3% 12/280 • Number of events 12	4.3% 12/279 • Number of events 13	5.0% 14/278 • Number of events 16	6.5% 4/62 • Number of events 5	4.8% 3/62 • Number of events 3
Infections and infestations Nasopharyngitis	8.2% 23/280 • Number of events 26	6.5% 18/279 • Number of events 19	4.3% 12/278 • Number of events 12	5.7% 8/141 • Number of events 8	9.3% 26/280 • Number of events 33	10.0% 28/279 • Number of events 31	5.8% 16/278 • Number of events 17	8.1% 5/62 • Number of events 6	3.2% 2/62 • Number of events 2
Infections and infestations Sinusitis	2.1% 6/280 • Number of events 6	1.8% 5/279 • Number of events 5	3.6% 10/278 • Number of events 10	1.4% 2/141 • Number of events 2	3.2% 9/280 • Number of events 11	4.3% 12/279 • Number of events 15	5.8% 16/278 • Number of events 16	3.2% 2/62 • Number of events 2	0.00% 0/62
Infections and infestations Upper respiratory tract infection	5.0% 14/280 • Number of events 17	4.3% 12/279 • Number of events 13	4.3% 12/278 • Number of events 14	4.3% 6/141 • Number of events 8	8.9% 25/280 • Number of events 31	5.7% 16/279 • Number of events 18	7.2% 20/278 • Number of events 29	8.1% 5/62 • Number of events 6	6.5% 4/62 • Number of events 5
Infections and infestations Urinary tract infection	2.9% 8/280 • Number of events 8	3.9% 11/279 • Number of events 11	2.2% 6/278 • Number of events 6	2.8% 4/141 • Number of events 4	4.6% 13/280 • Number of events 15	5.7% 16/279 • Number of events 18	5.0% 14/278 • Number of events 14	3.2% 2/62 • Number of events 2	8.1% 5/62 • Number of events 5
Investigations Lipase increased	1.1% 3/280 • Number of events 3	2.5% 7/279 • Number of events 8	1.8% 5/278 • Number of events 6	2.8% 4/141 • Number of events 4	2.1% 6/280 • Number of events 6	3.2% 9/279 • Number of events 11	3.2% 9/278 • Number of events 11	6.5% 4/62 • Number of events 5	3.2% 2/62 • Number of events 2
Metabolism and nutrition disorders Decreased appetite	5.0% 14/280 • Number of events 14	7.9% 22/279 • Number of events 23	2.9% 8/278 • Number of events 8	2.1% 3/141 • Number of events 3	5.4% 15/280 • Number of events 16	8.2% 23/279 • Number of events 24	3.2% 9/278 • Number of events 9	3.2% 2/62 • Number of events 3	4.8% 3/62 • Number of events 3
Musculoskeletal and connective tissue disorders Arthralgia	3.6% 10/280 • Number of events 10	2.9% 8/279 • Number of events 9	3.2% 9/278 • Number of events 12	2.1% 3/141 • Number of events 3	6.1% 17/280 • Number of events 18	4.3% 12/279 • Number of events 13	4.7% 13/278 • Number of events 19	4.8% 3/62 • Number of events 4	3.2% 2/62 • Number of events 2
Musculoskeletal and connective tissue disorders Back pain	3.2% 9/280 • Number of events 10	3.9% 11/279 • Number of events 11	2.9% 8/278 • Number of events 9	6.4% 9/141 • Number of events 9	5.0% 14/280 • Number of events 16	5.4% 15/279 • Number of events 16	4.3% 12/278 • Number of events 14	6.5% 4/62 • Number of events 4	8.1% 5/62 • Number of events 6
Musculoskeletal and connective tissue disorders Pain in extremity	2.9% 8/280 • Number of events 9	2.2% 6/279 • Number of events 6	2.9% 8/278 • Number of events 8	4.3% 6/141 • Number of events 7	4.6% 13/280 • Number of events 14	4.3% 12/279 • Number of events 12	5.4% 15/278 • Number of events 17	4.8% 3/62 • Number of events 4	6.5% 4/62 • Number of events 4
Nervous system disorders Dizziness	2.9% 8/280 • Number of events 9	5.4% 15/279 • Number of events 19	6.5% 18/278 • Number of events 23	1.4% 2/141 • Number of events 2	3.6% 10/280 • Number of events 11	6.8% 19/279 • Number of events 24	7.6% 21/278 • Number of events 30	0.00% 0/62	3.2% 2/62 • Number of events 2
Nervous system disorders Headache	3.2% 9/280 • Number of events 10	7.2% 20/279 • Number of events 26	8.6% 24/278 • Number of events 27	5.7% 8/141 • Number of events 9	5.0% 14/280 • Number of events 15	9.3% 26/279 • Number of events 36	9.0% 25/278 • Number of events 31	8.1% 5/62 • Number of events 6	9.7% 6/62 • Number of events 7
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.4% 4/280 • Number of events 4	1.8% 5/279 • Number of events 5	1.1% 3/278 • Number of events 3	5.0% 7/141 • Number of events 7	2.5% 7/280 • Number of events 8	2.5% 7/279 • Number of events 9	1.1% 3/278 • Number of events 3	6.5% 4/62 • Number of events 4	8.1% 5/62 • Number of events 5
Vascular disorders Hypertension	2.1% 6/280 • Number of events 6	2.5% 7/279 • Number of events 7	1.1% 3/278 • Number of events 3	4.3% 6/141 • Number of events 6	2.5% 7/280 • Number of events 7	2.9% 8/279 • Number of events 8	2.2% 6/278 • Number of events 6	1.6% 1/62 • Number of events 1	8.1% 5/62 • Number of events 5

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60