Trial Outcomes & Findings for A Study of LY2189265 Compared to Sitagliptin in Participants With Type 2 Diabetes Mellitus on Metformin (NCT NCT00734474)

Last Updated: 2015-04-20

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

1202 participants

Primary outcome timeframe

Baseline, 52 weeks

Results posted on

2015-04-20

Participant Flow

Participant milestones

Participant milestones
Measure	3.0 mg LY2189265 LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)	2.0 mg LY2189265 LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)	1.5 mg LY2189265 LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Overall Study STARTED	15	30	304	10	302	25	24	315	177
Overall Study Received at Least 1 Dose of Study Drug	15	30	304	10	302	25	24	315	177
Overall Study Entered Study Before Dose Decision Point	15	30	25	10	21	25	24	42	38
Overall Study Completed Up to Dose Decision Point	8	25	24	8	21	21	23	42	34
Overall Study Entered Study After Dose Decision Point	0	0	279	0	281	0	0	273	139
Overall Study Completed 26-Week Visit	0	0	258	2	268	2	2	270	124
Overall Study Completed 52-Week Visit	0	0	238	0	243	0	0	238	112
Overall Study COMPLETED	0	0	192	0	184	0	0	186	95
Overall Study NOT COMPLETED	15	30	112	10	118	25	24	129	82

Reasons for withdrawal

Reasons for withdrawal
Measure	3.0 mg LY2189265 LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)	2.0 mg LY2189265 LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)	1.5 mg LY2189265 LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Overall Study Entry Criteria Not Met	0	0	5	0	3	1	0	1	1
Overall Study Lost to Follow-up	1	0	13	0	11	1	0	9	4
Overall Study Withdrawal by Subject	2	1	18	0	24	2	0	36	21
Overall Study Physician Decision	0	0	4	1	11	0	0	9	9
Overall Study Adverse Event	4	4	63	1	64	0	1	65	39
Overall Study Protocol Violation	0	0	4	0	3	0	0	3	1
Overall Study Sponsor Decision, Arm Discontinued	8	25	0	8	0	21	23	0	0
Overall Study Sponsor Decision	0	0	0	0	2	0	0	0	0
Overall Study Death	0	0	1	0	0	0	0	2	1
Overall Study Lack of Efficacy	0	0	4	0	0	0	0	4	6

Baseline Characteristics

A Study of LY2189265 Compared to Sitagliptin in Participants With Type 2 Diabetes Mellitus on Metformin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	3.0 mg LY2189265 n=15 Participants LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)	2.0 mg LY2189265 n=30 Participants LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=10 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 n=25 Participants LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 n=24 Participants LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin n=177 Participants Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Total n=1202 Participants Total of all reporting groups
Age, Continuous	52.81 years STANDARD_DEVIATION 10.66 • n=5 Participants	52.56 years STANDARD_DEVIATION 10.95 • n=7 Participants	53.66 years STANDARD_DEVIATION 10.02 • n=5 Participants	55.38 years STANDARD_DEVIATION 8.71 • n=4 Participants	54.35 years STANDARD_DEVIATION 9.81 • n=21 Participants	54.70 years STANDARD_DEVIATION 9.72 • n=8 Participants	56.51 years STANDARD_DEVIATION 6.56 • n=8 Participants	53.75 years STANDARD_DEVIATION 10.27 • n=24 Participants	54.91 years STANDARD_DEVIATION 9.05 • n=42 Participants	54.09 years STANDARD_DEVIATION 9.85 • n=42 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	22 Participants n=7 Participants	158 Participants n=5 Participants	7 Participants n=4 Participants	168 Participants n=21 Participants	12 Participants n=8 Participants	15 Participants n=8 Participants	164 Participants n=24 Participants	87 Participants n=42 Participants	643 Participants n=42 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	8 Participants n=7 Participants	146 Participants n=5 Participants	3 Participants n=4 Participants	134 Participants n=21 Participants	13 Participants n=8 Participants	9 Participants n=8 Participants	151 Participants n=24 Participants	90 Participants n=42 Participants	559 Participants n=42 Participants
Race/Ethnicity, Customized Aboriginal and/or Torres Strait Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	1 participants n=24 Participants	0 participants n=42 Participants	1 participants n=42 Participants
Race/Ethnicity, Customized African	1 participants n=5 Participants	3 participants n=7 Participants	16 participants n=5 Participants	0 participants n=4 Participants	12 participants n=21 Participants	2 participants n=8 Participants	0 participants n=8 Participants	7 participants n=24 Participants	9 participants n=42 Participants	50 participants n=42 Participants
Race/Ethnicity, Customized Caucasian	7 participants n=5 Participants	13 participants n=7 Participants	157 participants n=5 Participants	4 participants n=4 Participants	162 participants n=21 Participants	9 participants n=8 Participants	12 participants n=8 Participants	158 participants n=24 Participants	91 participants n=42 Participants	613 participants n=42 Participants
Race/Ethnicity, Customized East Asian	0 participants n=5 Participants	6 participants n=7 Participants	50 participants n=5 Participants	0 participants n=4 Participants	47 participants n=21 Participants	0 participants n=8 Participants	5 participants n=8 Participants	52 participants n=24 Participants	28 participants n=42 Participants	188 participants n=42 Participants
Race/Ethnicity, Customized Hispanic	7 participants n=5 Participants	8 participants n=7 Participants	54 participants n=5 Participants	6 participants n=4 Participants	51 participants n=21 Participants	14 participants n=8 Participants	6 participants n=8 Participants	67 participants n=24 Participants	38 participants n=42 Participants	251 participants n=42 Participants
Race/Ethnicity, Customized Native American	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	1 participants n=24 Participants	0 participants n=42 Participants	1 participants n=42 Participants
Race/Ethnicity, Customized West Asian (Indian sub-continent)	0 participants n=5 Participants	0 participants n=7 Participants	27 participants n=5 Participants	0 participants n=4 Participants	30 participants n=21 Participants	0 participants n=8 Participants	1 participants n=8 Participants	28 participants n=24 Participants	11 participants n=42 Participants	97 participants n=42 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	1 participants n=24 Participants	0 participants n=42 Participants	1 participants n=42 Participants
Region of Enrollment United States	9 participants n=5 Participants	17 participants n=7 Participants	73 participants n=5 Participants	4 participants n=4 Participants	83 participants n=21 Participants	10 participants n=8 Participants	7 participants n=8 Participants	80 participants n=24 Participants	46 participants n=42 Participants	329 participants n=42 Participants
Region of Enrollment Taiwan	0 participants n=5 Participants	1 participants n=7 Participants	19 participants n=5 Participants	0 participants n=4 Participants	18 participants n=21 Participants	0 participants n=8 Participants	3 participants n=8 Participants	20 participants n=24 Participants	12 participants n=42 Participants	73 participants n=42 Participants
Region of Enrollment Spain	0 participants n=5 Participants	0 participants n=7 Participants	10 participants n=5 Participants	0 participants n=4 Participants	11 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	11 participants n=24 Participants	4 participants n=42 Participants	36 participants n=42 Participants
Region of Enrollment Russian Federation	0 participants n=5 Participants	0 participants n=7 Participants	21 participants n=5 Participants	0 participants n=4 Participants	18 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	17 participants n=24 Participants	8 participants n=42 Participants	64 participants n=42 Participants
Region of Enrollment India	0 participants n=5 Participants	0 participants n=7 Participants	27 participants n=5 Participants	0 participants n=4 Participants	29 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	28 participants n=24 Participants	12 participants n=42 Participants	96 participants n=42 Participants
Region of Enrollment France	0 participants n=5 Participants	0 participants n=7 Participants	12 participants n=5 Participants	0 participants n=4 Participants	14 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	12 participants n=24 Participants	8 participants n=42 Participants	46 participants n=42 Participants
Region of Enrollment Mexico	3 participants n=5 Participants	3 participants n=7 Participants	32 participants n=5 Participants	5 participants n=4 Participants	30 participants n=21 Participants	10 participants n=8 Participants	6 participants n=8 Participants	35 participants n=24 Participants	27 participants n=42 Participants	151 participants n=42 Participants
Region of Enrollment Puerto Rico	1 participants n=5 Participants	2 participants n=7 Participants	12 participants n=5 Participants	0 participants n=4 Participants	5 participants n=21 Participants	3 participants n=8 Participants	0 participants n=8 Participants	10 participants n=24 Participants	7 participants n=42 Participants	40 participants n=42 Participants
Region of Enrollment Canada	0 participants n=5 Participants	0 participants n=7 Participants	13 participants n=5 Participants	0 participants n=4 Participants	11 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	12 participants n=24 Participants	6 participants n=42 Participants	42 participants n=42 Participants
Region of Enrollment Poland	1 participants n=5 Participants	0 participants n=7 Participants	20 participants n=5 Participants	0 participants n=4 Participants	23 participants n=21 Participants	2 participants n=8 Participants	2 participants n=8 Participants	23 participants n=24 Participants	12 participants n=42 Participants	83 participants n=42 Participants
Region of Enrollment Romania	1 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants	1 participants n=4 Participants	4 participants n=21 Participants	0 participants n=8 Participants	4 participants n=8 Participants	8 participants n=24 Participants	5 participants n=42 Participants	32 participants n=42 Participants
Region of Enrollment Germany	0 participants n=5 Participants	0 participants n=7 Participants	31 participants n=5 Participants	0 participants n=4 Participants	31 participants n=21 Participants	0 participants n=8 Participants	0 participants n=8 Participants	28 participants n=24 Participants	15 participants n=42 Participants	105 participants n=42 Participants
Region of Enrollment Korea, Republic of	0 participants n=5 Participants	5 participants n=7 Participants	27 participants n=5 Participants	0 participants n=4 Participants	25 participants n=21 Participants	0 participants n=8 Participants	2 participants n=8 Participants	31 participants n=24 Participants	15 participants n=42 Participants	105 participants n=42 Participants
Body Weight	85.09 kilograms STANDARD_DEVIATION 14.25 • n=5 Participants	86.56 kilograms STANDARD_DEVIATION 18.33 • n=7 Participants	86.67 kilograms STANDARD_DEVIATION 17.45 • n=5 Participants	89.48 kilograms STANDARD_DEVIATION 18.06 • n=4 Participants	86.22 kilograms STANDARD_DEVIATION 17.99 • n=21 Participants	88.84 kilograms STANDARD_DEVIATION 14.98 • n=8 Participants	81.94 kilograms STANDARD_DEVIATION 17.67 • n=8 Participants	85.97 kilograms STANDARD_DEVIATION 16.91 • n=24 Participants	87.07 kilograms STANDARD_DEVIATION 16.86 • n=42 Participants	86.38 kilograms STANDARD_DEVIATION 17.28 • n=42 Participants
Body Mass Index (BMI)	31.02 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 4.69 • n=5 Participants	31.45 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 4.88 • n=7 Participants	31.40 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 4.57 • n=5 Participants	33.89 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 4.44 • n=4 Participants	31.15 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 4.44 • n=21 Participants	32.53 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 4.61 • n=8 Participants	31.06 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 3.94 • n=8 Participants	31.02 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 4.20 • n=24 Participants	31.37 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 4.25 • n=42 Participants	31.27 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 4.39 • n=42 Participants
Glycosylated Hemoglobin (HbA1c)	7.95 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.11 • n=5 Participants	8.36 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.04 • n=7 Participants	8.12 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.05 • n=5 Participants	7.87 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.62 • n=4 Participants	8.19 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.11 • n=21 Participants	8.30 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.34 • n=8 Participants	7.82 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.80 • n=8 Participants	8.09 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.09 • n=24 Participants	8.10 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.14 • n=42 Participants	8.13 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.09 • n=42 Participants
Duration of Diabetes	6.79 years STANDARD_DEVIATION 6.34 • n=5 Participants	6.92 years STANDARD_DEVIATION 5.12 • n=7 Participants	6.95 years STANDARD_DEVIATION 5.50 • n=5 Participants	7.04 years STANDARD_DEVIATION 4.57 • n=4 Participants	7.34 years STANDARD_DEVIATION 4.92 • n=21 Participants	6.75 years STANDARD_DEVIATION 3.99 • n=8 Participants	6.74 years STANDARD_DEVIATION 4.20 • n=8 Participants	7.16 years STANDARD_DEVIATION 4.89 • n=24 Participants	6.96 years STANDARD_DEVIATION 5.43 • n=42 Participants	7.09 years STANDARD_DEVIATION 5.12 • n=42 Participants
Fasting Plasma Glucose	NA millimoles per liter (mmol/L) STANDARD_DEVIATION NA • n=5 Participants	NA millimoles per liter (mmol/L) STANDARD_DEVIATION NA • n=7 Participants	9.75 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.27 • n=5 Participants	NA millimoles per liter (mmol/L) STANDARD_DEVIATION NA • n=4 Participants	9.68 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.94 • n=21 Participants	NA millimoles per liter (mmol/L) STANDARD_DEVIATION NA • n=8 Participants	NA millimoles per liter (mmol/L) STANDARD_DEVIATION NA • n=8 Participants	9.56 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.80 • n=24 Participants	9.86 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.15 • n=42 Participants	NA millimoles per liter (mmol/L) STANDARD_DEVIATION NA • n=42 Participants

PRIMARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms who had evaluable HbA1c data. Last observation carried forward 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	Sitagliptin n=311 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=301 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=297 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Glycosylated Hemoglobin (HbA1c) Change From Baseline	-0.39 percentage of HbA1c Standard Error 0.06	-1.10 percentage of HbA1c Standard Error 0.06	-0.87 percentage of HbA1c Standard Error 0.06	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to 27.4 weeks

Population: All participants randomized before the dose decision point who had evaluable HbA1c data.

Change from baseline in HbA1c was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the decision point was 27.4 weeks.

Outcome measures

Outcome measures
Measure	Sitagliptin n=20 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=10 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=26 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=8 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 n=20 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 n=21 Participants LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 n=14 Participants LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin n=30 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) n=28 Participants Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at the Dose Decision Point	-1.49 percentage of HbA1c Standard Deviation 1.12	-1.09 percentage of HbA1c Standard Deviation 0.77	-1.25 percentage of HbA1c Standard Deviation 0.68	-0.98 percentage of HbA1c Standard Deviation 0.47	-1.02 percentage of HbA1c Standard Deviation 0.99	-0.94 percentage of HbA1c Standard Deviation 0.65	-0.70 percentage of HbA1c Standard Deviation 0.49	-0.76 percentage of HbA1c Standard Deviation 0.86	-0.06 percentage of HbA1c Standard Deviation 0.64	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks, 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable HbA1c data. Last observation carried forward 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	Sitagliptin n=311 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=301 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=297 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=176 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Glycosylated Hemoglobin (HbA1c) Change From Baseline 104 Weeks	-0.32 percentage of HbA1c Standard Error 0.06	-0.99 percentage of HbA1c Standard Error 0.06	-0.71 percentage of HbA1c Standard Error 0.07	NA percentage of HbA1c Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—
Glycosylated Hemoglobin (HbA1c) Change From Baseline 26 Weeks	-0.61 percentage of HbA1c Standard Error 0.05	-1.22 percentage of HbA1c Standard Error 0.05	-1.01 percentage of HbA1c Standard Error 0.06	0.03 percentage of HbA1c Standard Error 0.07	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 13, 26, 52, and 104 weeks

Population: All participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms randomized after the dose decision point who had evaluable HbA1c data. If there were no data after the date of randomization, the endpoint was considered missing.

Durability of effect on HbA1c was assessed by comparing the differences in mean change from baseline in HbA1c at 1 time point versus an earlier time point. Least squares (LS) means of change from baseline HbA1c data were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Sitagliptin n=314 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=303 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Durability of Change From Baseline in Glycosylated Hemoglobin (HbA1c) 26 Weeks Versus 13 Weeks (n=269, 269, 276, 136)	0.00 percentage of HbA1c Standard Error 0.04	-0.03 percentage of HbA1c Standard Error 0.04	0.02 percentage of HbA1c Standard Error 0.04	-0.14 percentage of HbA1c Standard Error 0.05	—	—	—	—	—	—
Durability of Change From Baseline in Glycosylated Hemoglobin (HbA1c) 52 Weeks Versus 26 Weeks (n=245, 254, 250)	0.24 percentage of HbA1c Standard Error 0.05	0.14 percentage of HbA1c Standard Error 0.05	0.16 percentage of HbA1c Standard Error 0.05	NA percentage of HbA1c Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—
Durability of Change From Baseline in Glycosylated Hemoglobin (HbA1c) 104 Weeks Versus 52 Weeks (n=194, 191, 190)	0.09 percentage of HbA1c Standard Error 0.06	0.13 percentage of HbA1c Standard Error 0.06	0.16 percentage of HbA1c Standard Error 0.06	NA percentage of HbA1c Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable fasting plasma glucose data. If there were no data after the date of randomization, the endpoint was considered missing.

Least squares (LS) means of change from baseline were calculated using 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	Sitagliptin n=308 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=297 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=296 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=176 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Fasting Blood Glucose Change From Baseline 26 Weeks (n=265, 271, 276, 135)	-0.97 millimoles per liter (mmol/L) Standard Error 0.11	-2.38 millimoles per liter (mmol/L) Standard Error 0.12	-1.97 millimoles per liter (mmol/L) Standard Error 0.12	-0.49 millimoles per liter (mmol/L) Standard Error 0.16	—	—	—	—	—	—
Fasting Blood Glucose Change From Baseline 52 Weeks (n=239, 247, 244)	-0.90 millimoles per liter (mmol/L) Standard Error 0.13	-2.38 millimoles per liter (mmol/L) Standard Error 0.13	-1.63 millimoles per liter (mmol/L) Standard Error 0.13	NA millimoles per liter (mmol/L) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—
Fasting Blood Glucose Change From Baseline 104 Weeks (n=190, 187, 181)	-0.47 millimoles per liter (mmol/L) Standard Error 0.15	-1.99 millimoles per liter (mmol/L) Standard Error 0.15	-1.39 millimoles per liter (mmol/L) Standard Error 0.15	NA millimoles per liter (mmol/L) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 104 weeks

Population: All participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms randomized after the dose decision point who had evaluable fasting insulin data. If there were no data after the date of randomization, the endpoint was considered missing.

Least squares (LS) means of change from baseline fasting insulin data were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Sitagliptin n=247 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=254 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=261 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=122 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Fasting Insulin Change From Baseline 26 Weeks (n=238, 249, 230, 115)	8.48 picomoles per liter (pmol/L) Standard Error 6.68	11.59 picomoles per liter (pmol/L) Standard Error 6.57	10.15 picomoles per liter (pmol/L) Standard Error 6.51	-6.92 picomoles per liter (pmol/L) Standard Error 9.24	—	—	—	—	—	—
Fasting Insulin Change From Baseline 52 Weeks (n=207, 218, 200)	4.18 picomoles per liter (pmol/L) Standard Error 6.01	10.57 picomoles per liter (pmol/L) Standard Error 5.95	12.95 picomoles per liter (pmol/L) Standard Error 5.88	NA picomoles per liter (pmol/L) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—
Fasting Insulin Change From Baseline 104 Weeks (n=187, 200, 183)	0.29 picomoles per liter (pmol/L) Standard Error 7.64	11.36 picomoles per liter (pmol/L) Standard Error 7.58	21.56 picomoles per liter (pmol/L) Standard Error 7.40	NA picomoles per liter (pmol/L) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to 27.4 weeks

Population: All participants randomized before the dose decision point who had evaluable body weight data.

Change from baseline in body weight was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the decision point was 27.4 weeks.

Outcome measures

Outcome measures
Measure	Sitagliptin n=23 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=14 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=30 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=9 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 n=20 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 n=22 Participants LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 n=17 Participants LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin n=35 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) n=33 Participants Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Change From Baseline in Body Weight at Dose Decision Point	-2.12 kilograms (kg) Standard Deviation 1.93	-3.32 kilograms (kg) Standard Deviation 3.37	-2.15 kilograms (kg) Standard Deviation 1.97	-2.23 kilograms (kg) Standard Deviation 1.63	-1.17 kilograms (kg) Standard Deviation 2.30	-1.53 kilograms (kg) Standard Deviation 1.88	-0.85 kilograms (kg) Standard Deviation 1.47	-0.43 kilograms (kg) Standard Deviation 1.78	-0.56 kilograms (kg) Standard Deviation 1.69	—

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable body weight data. Last observation carried forward 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 of change from baseline body weight were calculated using analysis of covariance (ANCOVA) and last observation carried forward (LOCF) imputation with country and treatment as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Sitagliptin n=314 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=303 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=299 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Body Weight Change From Baseline 26 Weeks	-1.46 kilograms (kg) Standard Error 0.18	-3.18 kilograms (kg) Standard Error 0.18	-2.63 kilograms (kg) Standard Error 0.19	-1.47 kilograms (kg) Standard Error 0.24	—	—	—	—	—	—
Body Weight Change From Baseline 52 Weeks	-1.53 kilograms (kg) Standard Error 0.22	-3.03 kilograms (kg) Standard Error 0.22	-2.60 kilograms (kg) Standard Error 0.23	NA kilograms (kg) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Body Weight Change From Baseline 104 Weeks	-1.75 kilograms (kg) Standard Error 0.25	-2.88 kilograms (kg) Standard Error 0.25	-2.39 kilograms (kg) Standard Error 0.26	NA kilograms (kg) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 13, 26, 52, and 104 weeks

Population: All participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms randomized after the dose decision point who had evaluable body weight data. If there were no data after the date of randomization, the endpoint was considered missing.

Durability of effect on body weight was assessed by comparing the differences in mean change from baseline in body weight at 1 time point versus an earlier time point. Least squares (LS) means of change from baseline body weight data were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Durability of Change From Baseline Body Weight 26 Weeks Versus 13 Weeks (n=271, 278, 282, 138)	-0.42 kilograms (kg) Standard Error 0.13	-0.53 kilograms (kg) Standard Error 0.14	-0.57 kilograms (kg) Standard Error 0.14	-0.37 kilograms (kg) Standard Error 0.18	—	—	—	—	—	—
Durability of Change From Baseline Body Weight 52 Weeks Versus 26 Weeks (n=246, 255, 253)	-0.04 kilograms (kg) Standard Error 0.18	0.17 kilograms (kg) Standard Error 0.18	0.06 kilograms (kg) Standard Error 0.18	NA kilograms (kg) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—
Durability of Change From Baseline Body Weight 104 Weeks Versus 26 Weeks (n=197, 192, 191)	-0.39 kilograms (kg) Standard Error 0.23	0.42 kilograms (kg) Standard Error 0.23	0.32 kilograms (kg) Standard Error 0.24	NA kilograms (kg) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable waist circumference data. If there were no data after the date of randomization, the endpoint was considered missing.

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	Sitagliptin n=312 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=299 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=301 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=175 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Waist Circumference Change From Baseline 26 Weeks (n=266, 273, 277, 138)	-1.45 centimeters (cm) Standard Error 0.24	-2.89 centimeters (cm) Standard Error 0.24	-1.78 centimeters (cm) Standard Error 0.24	-1.20 centimeters (cm) Standard Error 0.32	—	—	—	—	—	—
Waist Circumference Change From Baseline 52 Weeks (n=238, 250, 247)	-1.45 centimeters (cm) Standard Error 0.29	-2.91 centimeters (cm) Standard Error 0.29	-2.05 centimeters (cm) Standard Error 0.29	NA centimeters (cm) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Waist Circumference Change From Baseline 104 Weeks (n=192, 189, 188)	-1.20 centimeters (cm) Standard Error 0.35	-2.57 centimeters (cm) Standard Error 0.35	-1.75 centimeters (cm) Standard Error 0.35	NA centimeters (cm) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 104 weeks

The percentage of participants achieving HbA1c levels \<7.0% and ≤6.5% was analyzed using a logistic regression model and last observation carried forward (LOCF) imputation with baseline, country, and treatment as factors included in the model.

Outcome measures

Outcome measures
Measure	Sitagliptin n=312 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=297 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=176 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5% ≤6.5% at 52 Weeks	19.2 percentage of participants	41.7 percentage of participants	29.0 percentage of participants	NA percentage of participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5% <7.0% at 26 Weeks	37.8 percentage of participants	60.9 percentage of participants	55.2 percentage of participants	21.0 percentage of participants	—	—	—	—	—	—
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5% <7.0% at 52 Weeks	33.0 percentage of participants	57.6 percentage of participants	48.8 percentage of participants	NA percentage of participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5% <7.0% at 104 Weeks	31.1 percentage of participants	54.3 percentage of participants	44.8 percentage of participants	NA percentage of participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5% ≤6.5% at 26 Weeks	21.8 percentage of participants	46.7 percentage of participants	31.0 percentage of participants	12.5 percentage of participants	—	—	—	—	—	—
Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5% ≤6.5% at 104 Weeks	14.1 percentage of participants	39.1 percentage of participants	24.2 percentage of participants	NA percentage of participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 26 and 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms.

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

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Incidence of Hypoglycemic Episodes Severe HE, 26 Weeks	0 participants	0 participants	0 participants	0 participants	—	—	—	—	—	—
Incidence of Hypoglycemic Episodes Severe HE, 104 Weeks	0 participants	0 participants	0 participants	NA participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Incidence of Hypoglycemic Episodes Documented Symptomatic HE, 26 Weeks	10 participants	17 participants	8 participants	2 participants	—	—	—	—	—	—
Incidence of Hypoglycemic Episodes Documented Symptomatic HE, 104 Weeks	18 participants	33 participants	19 participants	NA participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Incidence of Hypoglycemic Episodes Asymptomatic HE, 26 Weeks	0 participants	5 participants	5 participants	0 participants	—	—	—	—	—	—
Incidence of Hypoglycemic Episodes Asymptomatic HE, 104 Weeks	3 participants	9 participants	9 participants	NA participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Incidence of Hypoglycemic Episodes Nocturnal HE, 26 Weeks	2 participants	7 participants	5 participants	0 participants	—	—	—	—	—	—
Incidence of Hypoglycemic Episodes Nocturnal HE, 104 Weeks	10 participants	14 participants	13 participants	NA participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Incidence of Hypoglycemic Episodes Probable HE, 26 Weeks	2 participants	5 participants	0 participants	0 participants	—	—	—	—	—	—
Incidence of Hypoglycemic Episodes Probable HE, 104 Weeks	6 participants	6 participants	2 participants	NA participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 26 and 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms.

Hypoglycemic episodes (HE) were classified as severe (defined as episodes requiring assistance from another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia and has a plasma glucose level of ≤3.9 millimoles per liter \[mmol/L\]), asymptomatic (defined as episodes not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of ≤3.9 mmol/L), nocturnal (defined as any episode that occurred between bedtime and waking), or probable symptomatic (defined as episodes during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of HE is summarized cumulatively.

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Rate of Hypoglycemic Episodes Severe HE, 26 Weeks	0.0 episodes per participant per year Standard Deviation 0.0	0.0 episodes per participant per year Standard Deviation 0.0	0.0 episodes per participant per year Standard Deviation 0.0	0.0 episodes per participant per year Standard Deviation 0.0	—	—	—	—	—	—
Rate of Hypoglycemic Episodes Severe HE, 104 Weeks	0.0 episodes per participant per year Standard Deviation 0.0	0.0 episodes per participant per year Standard Deviation 0.0	0.0 episodes per participant per year Standard Deviation 0.0	NA episodes per participant per year Standard Deviation NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Rate of Hypoglycemic Episodes Documented Symptomatic HE, 26 Weeks	0.1 episodes per participant per year Standard Deviation 0.7	0.3 episodes per participant per year Standard Deviation 1.5	0.1 episodes per participant per year Standard Deviation 0.9	0.1 episodes per participant per year Standard Deviation 0.9	—	—	—	—	—	—
Rate of Hypoglycemic Episodes Documented Symptomatic HE, 104 Weeks	0.2 episodes per participant per year Standard Deviation 1.4	0.2 episodes per participant per year Standard Deviation 0.9	0.2 episodes per participant per year Standard Deviation 1.9	NA episodes per participant per year Standard Deviation NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Rate of Hypoglycemic Episodes Asymptomatic HE, 26 Weeks	0.0 episodes per participant per year Standard Deviation 0.0	0.1 episodes per participant per year Standard Deviation 0.8	0.1 episodes per participant per year Standard Deviation 0.5	0.0 episodes per participant per year Standard Deviation 0.0	—	—	—	—	—	—
Rate of Hypoglycemic Episodes Asymptomatic HE, 104 Weeks	0.0 episodes per participant per year Standard Deviation 0.1	0.1 episodes per participant per year Standard Deviation 0.4	0.0 episodes per participant per year Standard Deviation 0.2	NA episodes per participant per year Standard Deviation NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Rate of Hypoglycemic Episodes Nocturnal HE, 26 Weeks	0.0 episodes per participant per year Standard Deviation 0.4	0.1 episodes per participant per year Standard Deviation 0.9	0.1 episodes per participant per year Standard Deviation 0.6	0.0 episodes per participant per year Standard Deviation 0.0	—	—	—	—	—	—
Rate of Hypoglycemic Episodes Nocturnal HE, 104 Weeks	0.1 episodes per participant per year Standard Deviation 0.5	0.1 episodes per participant per year Standard Deviation 0.5	0.0 episodes per participant per year Standard Deviation 0.2	NA episodes per participant per year Standard Deviation NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Rate of Hypoglycemic Episodes Probable Symptomatic HE, 26 Weeks	0.0 episodes per participant per year Standard Deviation 0.2	0.0 episodes per participant per year Standard Deviation 0.4	0.0 episodes per participant per year Standard Deviation 0.0	0.0 episodes per participant per year Standard Deviation 0.0	—	—	—	—	—	—
Rate of Hypoglycemic Episodes Probable Symptomatic HE, 104 Weeks	0.0 episodes per participant per year Standard Deviation 0.1	0.0 episodes per participant per year Standard Deviation 0.1	0.0 episodes per participant per year Standard Deviation 0.0	NA episodes per participant per year Standard Deviation NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 104 weeks

Population: All participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms randomized after the dose decision point and who had evaluable HOMA2 data. If there were no data after the date of randomization, the endpoint was considered missing.

The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-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 population for both HOMA2-%B and HOMA2-%S were set at 100%. Least squares (LS) means of change from baseline of C-peptide based HOMA2-%B and HOMA2-%S 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	Sitagliptin n=238 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=242 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=251 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=115 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Beta Cell Function and Insulin Sensitivity (HOMA2) HOMA2-%B, 26 Weeks (n=206, 226, 206, 84)	10.81 HOMA2-% Standard Error 2.66	32.28 HOMA2-% Standard Error 2.67	26.98 HOMA2-% Standard Error 2.60	1.60 HOMA2-% Standard Error 4.02	—	—	—	—	—	—
Beta Cell Function and Insulin Sensitivity (HOMA2) HOMA2-%B, 52 Weeks (n=188, 198, 180)	6.66 HOMA2-% Standard Error 2.53	33.57 HOMA2-% Standard Error 2.51	22.30 HOMA2-% Standard Error 2.47	NA HOMA2-% Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—
Beta Cell Function and Insulin Sensitivity (HOMA2) HOMA2-%B, 104 Weeks (n=148, 154, 134)	1.47 HOMA2-% Standard Error 3.15	30.89 HOMA2-% Standard Error 3.05	19.11 HOMA2-% Standard Error 3.00	NA HOMA2-% Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—
Beta Cell Function and Insulin Sensitivity (HOMA2) HOMA2-%S, 26 Weeks (n=206, 226, 206, 84)	2.29 HOMA2-% Standard Error 2.33	5.75 HOMA2-% Standard Error 2.34	0.78 HOMA2-% Standard Error 2.28	9.82 HOMA2-% Standard Error 3.50	—	—	—	—	—	—
Beta Cell Function and Insulin Sensitivity (HOMA2) HOMA2-%S, 52 Weeks (n=188, 198, 180)	4.25 HOMA2-% Standard Error 2.37	4.69 HOMA2-% Standard Error 2.35	2.28 HOMA2-% Standard Error 2.32	NA HOMA2-% Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—
Beta Cell Function and Insulin Sensitivity (HOMA2) HOMA2-%S, 104 Weeks (n=148, 154, 134)	5.61 HOMA2-% Standard Error 3.11	3.82 HOMA2-% Standard Error 3.00	-0.12 HOMA2-% Standard Error 2.95	NA HOMA2-% Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for participants who received Placebo at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 26 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms.

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 1 or more TEAEs is summarized cumulatively. 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	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Number of Participants With Treatment-emergent Adverse Events at 26 Weeks	185 participants	208 participants	204 participants	111 participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: All randomized participants in the LY2189265 and active comparator (Sitagliptin) arms.

Outcome measures

Outcome measures
Measure	Sitagliptin n=304 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=15 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=30 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=10 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 n=25 Participants LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 n=24 Participants LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Number of Participants With Treatment-emergent Adverse Events at 52 Weeks	233 participants	9 participants	20 participants	8 participants	231 participants	15 participants	10 participants	219 participants	—	—

SECONDARY outcome

Timeframe: Baseline through 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms.

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Number of Participants With Treatment-emergent Adverse Events at 104 Weeks	242 participants	259 participants	255 participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 26 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms with baseline value not in the specified direction of treatment-emergent abnormality and at least 1 postbaseline result.

The number of participants with treatment-emergent abnormal laboratory results (defined as abnormalities that first occur after baseline) was summarized cumulatively for alkaline phosphatase, alanine aminotransferase or serum glutamic pyruvic transaminase (ALT/SGPT), amylase (pancreatic and total), aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT), basophils, bilirubin (direct and total), calcitonin, chloride, creatine phosphokinase (CPK), creatinine, creatinine clearance, eosinophils, erythrocytes, gamma glutamyltransferase (GGT), hematocrit, hemoglobin, leukocytes, lipase, lymphocytes, mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), monocytes, neutrophils, platelets, potassium, sodium, urea nitrogen, and urine microalbumin-to-creatinine ratio (UMCR).

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Alkaline Phosphatase (n=276, 258, 281, 162)	12 participants	9 participants	3 participants	3 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks ALT/SGPT (n=232, 237, 244, 128)	25 participants	18 participants	24 participants	8 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Amylase Pancreatic, High (n=283, 277, 295, 160)	42 participants	54 participants	55 participants	18 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Amylase Total (n=266, 265, 277, 143)	27 participants	33 participants	33 participants	13 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks AST/SGOT (n=273, 269, 284, 148)	18 participants	14 participants	12 participants	7 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Basophils, High (n=268, 259, 278, 163)	1 participants	1 participants	0 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Basophils, Low (n=269, 259, 278, 163)	0 participants	0 participants	0 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Bilirubin Direct, High (n=295, 291, 307, 171)	1 participants	1 participants	1 participants	2 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Bilirubin Total, High (n=295, 290, 305, 168)	4 participants	2 participants	4 participants	1 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Calcitonin, High (n=226, 233, 230, 113)	2 participants	1 participants	2 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Chloride, High (n=299, 293, 310, 174)	0 participants	0 participants	1 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Chloride, Low (n=299, 293, 308, 174)	1 participants	1 participants	2 participants	1 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks CPK, High (n=273, 262, 276, 156	30 participants	29 participants	20 participants	7 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Creatinine, High (n=294, 285, 303, 172)	5 participants	7 participants	10 participants	5 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Creatinine Clearance, High (n=164, 186, 180, 107)	26 participants	17 participants	28 participants	25 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Creatinine Clearance, Low (n=292, 278,303,168)	12 participants	11 participants	17 participants	6 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Eosinophils, High (n=258, 256, 275, 157)	6 participants	4 participants	11 participants	2 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Eosinophils, Low (n=269, 259, 278, 163)	0 participants	0 participants	0 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Erythrocyte Count, High (n=279, 272, 287, 164)	0 participants	1 participants	1 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Erythrocyte Count, Low (n=274, 268, 280, 161)	7 participants	12 participants	7 participants	3 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks GGT, High (n=234, 240, 245, 144)	23 participants	9 participants	11 participants	10 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Hematocrit, High (n=273, 265, 279, 161)	1 participants	1 participants	1 participants	2 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Hematocrit, Low (n=256, 242, 259, 157)	6 participants	13 participants	10 participants	5 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Hemoglobin, High (n=278, 271, 289, 164)	1 participants	1 participants	1 participants	2 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Hemoglobin, Low (n=262, 249, 265, 162)	5 participants	13 participants	16 participants	3 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Leukocyte Count, High (n=272, 265, 286, 165)	1 participants	3 participants	6 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Leukocyte Count, Low (n=272, 262, 280, 165)	4 participants	2 participants	3 participants	1 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Lipase, High (n=255, 248, 269, 147)	97 participants	109 participants	92 participants	37 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Lymphocytes, High (n=249, 253, 269, 161)	6 participants	5 participants	9 participants	3 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Lymphocytes, Low (n=265, 258, 273, 159)	4 participants	3 participants	3 participants	2 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks MCHC, High (n=274, 265, 280, 163)	0 participants	0 participants	0 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks MCHC, Low (n=273, 263, 279, 163)	0 participants	0 participants	2 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks MCV, High (n=261, 248, 263, 156)	14 participants	19 participants	12 participants	5 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks MCV, Low (n=264, 252, 275, 162)	2 participants	3 participants	2 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Monocytes, High (n=266, 258, 274, 163)	3 participants	1 participants	0 participants	1 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Monocytes, Low (n=265, 255, 274, 158)	8 participants	6 participants	5 participants	10 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Neutrophils, High (n=264, 255, 276, 161)	3 participants	4 participants	5 participants	1 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Neutrophils, Low (n=263, 251, 271, 162)	2 participants	2 participants	1 participants	1 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Platelet Count, High (n=265, 260, 281, 160)	1 participants	0 participants	0 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Platelet Count, Low (n=262, 252, 269, 154)	6 participants	2 participants	3 participants	3 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Potassium, High (n=297, 291, 307, 172)	5 participants	7 participants	2 participants	4 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Potassium, Low (n=298, 293, 308, 169)	3 participants	4 participants	6 participants	1 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Sodium, High (n=291, 291, 307, 170)	4 participants	3 participants	4 participants	4 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Sodium, Low (n=298, 292, 305, 174)	4 participants	2 participants	1 participants	1 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks Urea Nitrogen, High (n=287, 282, 305, 169)	13 participants	11 participants	17 participants	5 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks UMCR, High (n=217, 204, 232, 130)	13 participants	18 participants	9 participants	5 participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms with baseline value not in the specified direction of treatment-emergent abnormality and at least 1 postbaseline result.

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Alkaline Phosphatase, High (n=276, 258, 281)	16 participants	10 participants	6 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks ALT/SGPT, High (n=232, 237, 244)	28 participants	25 participants	27 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Amylase Pancreatic, High (n=283, 277, 295)	55 participants	67 participants	70 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Amylase Total, High (n=266, 265, 277)	36 participants	38 participants	42 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks AST/SGOT, High (n=273, 269, 284)	25 participants	15 participants	19 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Basophils, High (n=276, 268, 287)	1 participants	1 participants	0 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Basophils, Low (n=277, 268, 287)	0 participants	0 participants	0 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Bilirubin Direct, High (n=295, 291, 307)	2 participants	1 participants	1 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Bilirubin Total, High (n=295, 290, 305)	5 participants	2 participants	6 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Calcitonin, High (n=233, 239, 235)	2 participants	4 participants	2 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Chloride, High (n=299, 293, 310)	0 participants	0 participants	1 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Chloride, Low (n=299, 293, 308)	2 participants	1 participants	2 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks CPK, High (n=273, 262, 276)	43 participants	38 participants	28 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Creatinine, High (n=294, 285, 303)	6 participants	9 participants	10 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks MCHC, Low (n=280, 272, 290)	3 participants	2 participants	3 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Creatinine Clearance, High (n=164, 186, 180)	29 participants	23 participants	30 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Creatinine Clearance, Low (n=292, 278, 303)	15 participants	18 participants	20 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Eosinophils, High (n=265, 265, 283)	10 participants	11 participants	14 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Eosinophils, Low (n=277, 268, 287)	0 participants	0 participants	0 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Erythrocyte Count, High (n=283, 276, 292)	1 participants	3 participants	1 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Erythrocyte Count, Low (n=278, 272, 285)	11 participants	15 participants	9 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks GGT, High (n=234, 240, 245)	34 participants	10 participants	14 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Hematocrit, High (n=280, 274, 290)	2 participants	3 participants	2 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Hematocrit, Low (n=262, 251, 269)	11 participants	21 participants	13 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Hemoglobin, High (n=282, 275, 294)	1 participants	3 participants	1 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Hemoglobin, Low (n=265, 253, 269)	11 participants	21 participants	19 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Leukocyte Count, High (n=277, 270, 292)	3 participants	7 participants	6 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Leukocyte Count, Low (n=277, 267, 284)	9 participants	5 participants	3 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Lipase, High (n=255, 248, 269)	110 participants	124 participants	111 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Lymphocytes, High (n=257, 262, 278)	11 participants	12 participants	15 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Lymphocytes, Low (n=273, 266, 280)	11 participants	4 participants	4 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks MCHC, High (n=281, 274, 291)	0 participants	0 participants	0 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks MCV, High (n=267, 256, 273)	19 participants	25 participants	18 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks MCV, Low (n=270, 261, 286)	4 participants	3 participants	2 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Monocytes, High (n=274, 267, 283)	5 participants	1 participants	0 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Monocytes, Low (n=271, 264, 282)	15 participants	8 participants	9 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Neutrophils, High (n=272, 263, 285)	7 participants	8 participants	7 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Neutrophils, Low (n=271, 260, 279)	6 participants	6 participants	2 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Platelet Count, High (n=272, 267, 287)	2 participants	0 participants	2 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Platelet Count, Low (n=269, 259, 275)	8 participants	4 participants	5 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Potassium, High (n=297, 291, 307)	5 participants	10 participants	5 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Potassium, Low (n=298, 293, 308)	5 participants	6 participants	7 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Sodium, High (n=291, 291, 307)	4 participants	5 participants	8 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Sodium, Low (n=298, 292, 305)	4 participants	3 participants	1 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks Urea Nitrogen, High (n=287, 282, 305)	21 participants	14 participants	19 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks UMCR, High (n=223, 212, 238)	18 participants	33 participants	21 participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 104 weeks

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Calcitonin, High (n=233, 239, 235)	4 participants	5 participants	3 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Chloride, High (n=299, 293, 310)	1 participants	0 participants	2 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Alkaline Phosphate, High (n=276, 258, 281)	20 participants	13 participants	11 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks ALT/SGPT, High (n=232, 237, 244)	39 participants	29 participants	37 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Amylase Pancreatic, High (n=283, 277, 295)	61 participants	81 participants	78 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Amylase Total, High (n=266, 265, 277)	43 participants	44 participants	55 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks AST/SGOT, High (n=273, 269, 284)	36 participants	21 participants	27 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Basophils, High (n=276, 268, 288)	1 participants	1 participants	0 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Basophils, Low (n=277, 268, 288)	0 participants	0 participants	0 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Bilirubin Direct, High (n=295, 291, 307)	3 participants	2 participants	1 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Bilirubin Total, High (n=295, 290, 305)	6 participants	3 participants	8 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Chloride, Low (n=299, 293, 308)	3 participants	3 participants	2 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks CPK, High (n=273, 262, 276)	54 participants	52 participants	41 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Creatinine, High (n=294, 285, 303)	9 participants	11 participants	16 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Creatinine Clearance, High (n=164, 186, 180)	34 participants	26 participants	32 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Creatinine Clearance, Low (n=292, 278, 303)	20 participants	24 participants	25 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Eosinophils, High (n=265, 265, 284)	14 participants	12 participants	22 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Eosinophils, Low (n=277, 268, 288)	0 participants	0 participants	0 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Erythrocyte Count, High (n=283, 276, 292)	1 participants	3 participants	2 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Erythrocyte Count, Low (n=278, 272, 285)	19 participants	18 participants	14 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks GGT, High (n=234, 240, 245)	45 participants	16 participants	24 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Hematocrit, High (n=280, 274, 290)	3 participants	3 participants	6 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Hematocrit, Low (n=262, 251, 269)	29 participants	30 participants	24 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Hemoglobin, High (n=282, 275, 294)	2 participants	4 participants	3 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Hemoglobin, Low (n=265, 253, 269)	25 participants	30 participants	28 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Leukocyte Count, High (n=277, 270, 292)	8 participants	13 participants	9 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Leukocyte Count, Low (n=277, 267, 284)	14 participants	9 participants	7 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Lipase, High (n=255, 248, 269)	126 participants	142 participants	132 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Lymphocytes, High (n=257, 262, 279)	21 participants	19 participants	20 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Lymphocytes, Low (n=273, 266, 281)	12 participants	5 participants	9 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks MCHC, High (n=281, 274, 291)	0 participants	0 participants	0 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks MCHC, Low (n=280, 272, 290)	5 participants	5 participants	4 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks MCV, High (n=267, 256, 273)	25 participants	39 participants	25 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks MCV, Low (n=270, 261, 286)	4 participants	9 participants	3 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Monocytes, High (n=274, 267, 284)	11 participants	3 participants	1 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Monocytes, Low (n=271, 264, 283)	17 participants	10 participants	14 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Neutrophils, High (n=272, 263, 286)	13 participants	15 participants	12 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Neutrophils, Low (n=271, 260, 280)	10 participants	10 participants	6 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Platelet Count, High (n=273, 268, 287)	3 participants	2 participants	3 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Platelet Count, Low (n=270, 260, 275)	8 participants	8 participants	7 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Potassium, High (n=297, 291, 307)	8 participants	14 participants	9 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Potassium, Low (n=298, 293, 308)	5 participants	8 participants	8 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Sodium, High (n=291, 291, 307)	6 participants	10 participants	10 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Sodium, Low (n=298, 292, 305)	5 participants	5 participants	1 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks Urea Nitrogen, High (n=287, 282, 305)	29 participants	17 participants	29 participants	—	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks UMCR, High (n=223, 212, 239)	30 participants	38 participants	27 participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 26 and 104 weeks

The number of participants with treatment-emergent abnormal lipid test (cholesterol, high density lipoprotein cholesterol \[HDL-C\], low density lipoprotein cholesterol \[LDL-C\], and triglycerides \[TG\]) results (defined as lipid test abnormalities that first occurred after baseline) is summarized cumulatively.

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Number of Participants With Treatment-emergent Abnormal Lipid Tests Cholesterol, High, 26 Weeks (n=144, 158, 139, 58)	20 participants	16 participants	21 participants	8 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Lipid Tests Cholesterol, High, 104 Weeks (n=151, 164, 146)	34 participants	34 participants	29 participants	NA participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Lipid Tests HDL-C, High, 26 Weeks (n=197, 201, 189, 78)	0 participants	1 participants	0 participants	0 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Lipid Tests HDL-C, Low, 26 Weeks (n=127, 137, 129, 52)	8 participants	9 participants	13 participants	1 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Lipid Tests HDL-C, High, 104 Weeks (n=206, 212, 199)	2 participants	2 participants	1 participants	NA participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Lipid Tests HDL-C, Low, 104 Weeks (n=134, 143, 138)	13 participants	13 participants	20 participants	NA participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Lipid Tests LDL-C, High, 26 Weeks (n=155, 163, 150, 61)	19 participants	15 participants	11 participants	7 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Lipid Tests LDL-C, High, 104 Weeks (n=163, 170, 157)	29 participants	31 participants	23 participants	NA participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Lipid Tests TG, High, 26 Weeks (n=163, 174, 156, 64)	10 participants	6 participants	13 participants	2 participants	—	—	—	—	—	—
Number of Participants With Treatment-emergent Abnormal Lipid Tests TG, High, 104 Weeks (n=170, 183, 166)	15 participants	13 participants	22 participants	NA participants Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline up to 27.4 weeks

Population: All participants randomized before the dose decision point who had evaluable sitting pulse rate data.

Sitting pulse rate was measured at the time that the dose decision was made (dose decision point). Change from baseline in pulse rate was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the decision point was 27.4 weeks.

Outcome measures

Outcome measures
Measure	Sitagliptin n=23 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=14 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=30 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=9 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 n=20 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 n=22 Participants LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 n=17 Participants LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin n=35 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) n=33 Participants Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Change From Baseline in Pulse Rate at Dose Decision Point	2.39 beats per minute (bpm) Standard Deviation 7.88	6.63 beats per minute (bpm) Standard Deviation 7.28	3.43 beats per minute (bpm) Standard Deviation 10.14	3.34 beats per minute (bpm) Standard Deviation 9.88	-1.63 beats per minute (bpm) Standard Deviation 8.03	1.91 beats per minute (bpm) Standard Deviation 6.18	1.05 beats per minute (bpm) Standard Deviation 9.44	-0.16 beats per minute (bpm) Standard Deviation 8.07	1.81 beats per minute (bpm) Standard Deviation 7.90	—

SECONDARY outcome

Timeframe: Baseline up to 27.4 weeks

Population: All participants randomized before the dose decision point who had evaluable sitting SBP and DBP data.

Sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at the dose decision point. Change from baseline in DBP was 1 of the 4 measures included in the clinical utility index (CUI) used to evaluate the dose decision. The maximum duration of exposure to LY2189265, Sitagliptin, or Placebo (across all treatment arms) at the time of the decision point was 27.4 weeks.

Outcome measures

Outcome measures
Measure	Sitagliptin n=23 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=14 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=30 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=9 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 n=20 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 n=22 Participants LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 n=17 Participants LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin n=35 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) n=33 Participants Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Change From Baseline in Blood Pressure at Dose Decision Point Sitting SBP	-4.77 millimeters of mercury (mmHg) Standard Deviation 11.37	-8.85 millimeters of mercury (mmHg) Standard Deviation 12.92	-4.63 millimeters of mercury (mmHg) Standard Deviation 15.28	-2.00 millimeters of mercury (mmHg) Standard Deviation 9.94	-6.21 millimeters of mercury (mmHg) Standard Deviation 19.13	0.40 millimeters of mercury (mmHg) Standard Deviation 11.51	1.67 millimeters of mercury (mmHg) Standard Deviation 10.18	-2.16 millimeters of mercury (mmHg) Standard Deviation 10.62	-0.61 millimeters of mercury (mmHg) Standard Deviation 14.75	—
Change From Baseline in Blood Pressure at Dose Decision Point Sitting DBP	-1.20 millimeters of mercury (mmHg) Standard Deviation 4.67	-1.21 millimeters of mercury (mmHg) Standard Deviation 7.47	-1.17 millimeters of mercury (mmHg) Standard Deviation 6.32	-0.08 millimeters of mercury (mmHg) Standard Deviation 8.00	-3.18 millimeters of mercury (mmHg) Standard Deviation 10.13	-0.75 millimeters of mercury (mmHg) Standard Deviation 7.99	1.28 millimeters of mercury (mmHg) Standard Deviation 4.06	-1.11 millimeters of mercury (mmHg) Standard Deviation 6.65	-0.22 millimeters of mercury (mmHg) Standard Deviation 7.94	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks, 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable pulse data. If there were no data after the date of randomization, the endpoint was considered missing.

Sitting and standing pulse rate 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 covariate.

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Change From Baseline in Pulse Rate Sitting, 26 Weeks (n=271, 278, 283, 138)	-0.11 beats per minute (bpm) Standard Error 0.46	2.57 beats per minute (bpm) Standard Error 0.47	1.90 beats per minute (bpm) Standard Error 0.47	-0.22 beats per minute (bpm) Standard Error 0.65	—	—	—	—	—	—
Change From Baseline in Pulse Rate Sitting, 104 Weeks (n=197, 192, 191)	-0.78 beats per minute (bpm) Standard Error 0.53	2.28 beats per minute (bpm) Standard Error 0.53	2.77 beats per minute (bpm) Standard Error 0.54	NA beats per minute (bpm) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Change From Baseline in Pulse Rate Standing, 26 Weeks (n=271, 277, 281, 138)	-0.24 beats per minute (bpm) Standard Error 0.51	3.24 beats per minute (bpm) Standard Error 0.52	2.00 beats per minute (bpm) Standard Error 0.52	-0.17 beats per minute (bpm) Standard Error 0.71	—	—	—	—	—	—
Change From Baseline in Pulse Rate Standing, 104 Weeks (n=197, 192, 191)	-1.06 beats per minute (bpm) Standard Error 0.63	2.26 beats per minute (bpm) Standard Error 0.63	2.50 beats per minute (bpm) Standard Error 0.64	NA beats per minute (bpm) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks, 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable SBP and DBP data. If there were no data after the date of randomization, the endpoint was considered missing.

Sitting and standing systolic blood pressure (SBP) and 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	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Change From Baseline in Blood Pressure Sitting SBP, 26 Weeks (n=271, 278, 283, 138)	-1.94 millimeters of mercury (mmHg) Standard Error 0.66	-1.73 millimeters of mercury (mmHg) Standard Error 0.67	-1.40 millimeters of mercury (mmHg) Standard Error 0.67	1.12 millimeters of mercury (mmHg) Standard Error 0.92	—	—	—	—	—	—
Change From Baseline in Blood Pressure Sitting SBP, 104 Weeks (n=197, 192, 191)	0.02 millimeters of mercury (mmHg) Standard Error 0.82	-0.07 millimeters of mercury (mmHg) Standard Error 0.81	1.28 millimeters of mercury (mmHg) Standard Error 0.82	NA millimeters of mercury (mmHg) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Change From Baseline in Blood Pressure Sitting DBP, 26 Weeks (n=271, 278, 283, 138)	-1.06 millimeters of mercury (mmHg) Standard Error 0.42	-0.43 millimeters of mercury (mmHg) Standard Error 0.43	-0.20 millimeters of mercury (mmHg) Standard Error 0.43	0.68 millimeters of mercury (mmHg) Standard Error 0.58	—	—	—	—	—	—
Change From Baseline in Blood Pressure Sitting DBP, 104 Weeks (n=197, 192, 191)	-0.36 millimeters of mercury (mmHg) Standard Error 0.52	0.38 millimeters of mercury (mmHg) Standard Error 0.52	1.40 millimeters of mercury (mmHg) Standard Error 0.52	NA millimeters of mercury (mmHg) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Change From Baseline in Blood Pressure Standing SBP, 26 Weeks (n=271, 277, 281, 138)	-2.54 millimeters of mercury (mmHg) Standard Error 0.74	-1.53 millimeters of mercury (mmHg) Standard Error 0.76	-1.72 millimeters of mercury (mmHg) Standard Error 0.76	0.26 millimeters of mercury (mmHg) Standard Error 1.04	—	—	—	—	—	—
Change From Baseline in Blood Pressure Standing SBP, 104 Weeks (n=197, 192, 191)	-1.20 millimeters of mercury (mmHg) Standard Error 0.92	-1.30 millimeters of mercury (mmHg) Standard Error 0.92	0.17 millimeters of mercury (mmHg) Standard Error 0.93	NA millimeters of mercury (mmHg) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Change From Baseline in Blood Pressure Standing DBP, 26 Weeks (n=271, 277, 281, 138)	-1.36 millimeters of mercury (mmHg) Standard Error 0.47	-0.11 millimeters of mercury (mmHg) Standard Error 0.48	0.03 millimeters of mercury (mmHg) Standard Error 0.48	-0.52 millimeters of mercury (mmHg) Standard Error 0.66	—	—	—	—	—	—
Change From Baseline in Blood Pressure Standing DBP, 104 Weeks (n=197, 192, 191)	-0.67 millimeters of mercury (mmHg) Standard Error 0.58	-0.23 millimeters of mercury (mmHg) Standard Error 0.57	0.36 millimeters of mercury (mmHg) Standard Error 0.58	NA millimeters of mercury (mmHg) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 26 weeks, 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and comparator (Sitagliptin, Placebo/Sitagliptin) arms who had evaluable ECG data. If there were no data after the date of randomization, the endpoint was considered missing.

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	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=177 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval PR Interval, 26 Weeks (n=256, 261, 268, 132)	0.42 milliseconds (msec) Standard Error 0.65	2.94 milliseconds (msec) Standard Error 0.66	1.60 milliseconds (msec) Standard Error 0.66	2.24 milliseconds (msec) Standard Error 0.89	—	—	—	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval PR Interval, 104 Weeks (n=168, 170, 167)	3.19 milliseconds (msec) Standard Error 0.90	4.59 milliseconds (msec) Standard Error 0.90	3.06 milliseconds (msec) Standard Error 0.90	NA milliseconds (msec) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval QTcF Interval, 26 Weeks (n=258, 262, 268, 132)	-1.31 milliseconds (msec) Standard Error 0.73	-3.86 milliseconds (msec) Standard Error 0.75	-2.44 milliseconds (msec) Standard Error 0.75	1.76 milliseconds (msec) Standard Error 1.02	—	—	—	—	—	—
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval QTcF Interval, 104 Weeks (n=169, 170, 168)	-0.02 milliseconds (msec) Standard Error 0.83	-2.71 milliseconds (msec) Standard Error 0.84	-2.49 milliseconds (msec) Standard Error 0.84	NA milliseconds (msec) Standard Error NA Placebo treatment lasted through 26 weeks. Thus, there are no data for this treatment arm at this time point.	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks, and 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms who had evaluable IWQoL-Lite data. If there were no data after the date of randomization, the endpoint was considered missing.

The Impact of Weight on Quality of Life-Lite (IWQoL-Lite questionnaire) is an obesity-specific, 31-item questionnaire designed to measure the impact of weight on participants' quality of life. Items are scored on a 5-point numeric rating scale where 5 = "always true" and 1 = "never true". Items are summed into 6 scales (physical function \[11 items\], self-esteem \[7 items\], sexual life \[4 items\], public distress \[5 items\], work \[4 items\], and total score \[31 items\]) based on the average for the valid responses on that scale multiplied by the number of items on that scale (rounded to the nearest whole integer). Higher scores indicate lower levels of functioning (negative effects). Scores are linearly transformed to a 0 to 100 scale.

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Participant-reported Outcomes, Impact of Weight on Quality of Life-Lite (IWQoL-Lite) Total Score, Baseline (n=285, 284, 300)	83.97 units on a scale Standard Deviation 16.514	83.41 units on a scale Standard Deviation 16.031	82.55 units on a scale Standard Deviation 16.952	—	—	—	—	—	—	—
Participant-reported Outcomes, Impact of Weight on Quality of Life-Lite (IWQoL-Lite) Total Score, 52 Weeks (n=237, 252, 247)	86.25 units on a scale Standard Deviation 15.628	86.92 units on a scale Standard Deviation 14.972	86.31 units on a scale Standard Deviation 14.673	—	—	—	—	—	—	—
Participant-reported Outcomes, Impact of Weight on Quality of Life-Lite (IWQoL-Lite) Total Score, 104 Weeks (n=190, 190, 185)	86.93 units on a scale Standard Deviation 16.304	88.08 units on a scale Standard Deviation 15.555	87.47 units on a scale Standard Deviation 15.183	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 52 weeks, and 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms who had evaluable EQ-5D data. If there were no data after the date of randomization, the endpoint was considered missing.

The EQ-5D questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts. The first part allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a three level scale of 1-3 (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). The second part of the questionnaire consists of a 100-millimeter 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 state).

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Participant-reported Outcomes, EQ-5D EQ-5D, UK, Baseline (n=285, 281, 300)	0.84 units on a scale Standard Deviation 0.216	0.80 units on a scale Standard Deviation 0.222	0.82 units on a scale Standard Deviation 0.223	—	—	—	—	—	—	—
Participant-reported Outcomes, EQ-5D EQ-5D, UK, 52 Weeks (n=237, 250, 244)	0.85 units on a scale Standard Deviation 0.210	0.83 units on a scale Standard Deviation 0.211	0.84 units on a scale Standard Deviation 0.208	—	—	—	—	—	—	—
Participant-reported Outcomes, EQ-5D EQ-5D, UK, 104 Weeks (n=189, 190, 185)	0.86 units on a scale Standard Deviation 0.198	0.84 units on a scale Standard Deviation 0.203	0.86 units on a scale Standard Deviation 0.184	—	—	—	—	—	—	—
Participant-reported Outcomes, EQ-5D VAS, Baseline (n=285, 284, 301)	76.85 units on a scale Standard Deviation 15.363	75.57 units on a scale Standard Deviation 15.798	75.35 units on a scale Standard Deviation 16.001	—	—	—	—	—	—	—
Participant-reported Outcomes, EQ-5D VAS, 52 Weeks (n=238, 251, 245)	78.79 units on a scale Standard Deviation 14.567	78.93 units on a scale Standard Deviation 13.352	78.22 units on a scale Standard Deviation 13.839	—	—	—	—	—	—	—
Participant-reported Outcomes, EQ-5D VAS, 104 Weeks (n=189, 190, 185)	81.34 units on a scale Standard Deviation 13.708	79.66 units on a scale Standard Deviation 13.820	78.52 units on a scale Standard Deviation 14.114	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 52 and 104 weeks

Population: All randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) and active comparator (Sitagliptin) arms.

The number of visits to the emergency room (ER) is summarized cumulatively.

Outcome measures

Outcome measures
Measure	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=304 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Resource Utilization 52 Weeks	NA events Data were not summarized cumulatively for this outcome measure.	NA events Data were not summarized cumulatively for this outcome measure.	NA events Data were not summarized cumulatively for this outcome measure.	—	—	—	—	—	—	—
Resource Utilization 104 Weeks	NA events Data were not summarized cumulatively for this outcome measure.	NA events Data were not summarized cumulatively for this outcome measure.	NA events Data were not summarized cumulatively for this outcome measure.	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: Randomized participants in the selected (1.5 mg, 0.75 mg LY2189265) who had blood samples collected for PK assessments.

Pharmacokinetic (PK) parameter estimates from LY2189265 concentration data were obtained using a 2-compartment population PK model with first order absorption. Area under the plasma-concentration curve from 0 to 168 hours, steady state (AUC0-168h, ss) of LY2189265 is summarized.

Outcome measures

Outcome measures
Measure	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=69 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=60 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Pharmacokinetics of LY2189265: Area Under the Concentration-Time Curve	—	13378 nanograms times hours per milliliter Standard Deviation 6100	7246 nanograms times hours per milliliter Standard Deviation 3304	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline through 104 weeks

Population: All randomized participants in the LY2189265 arms who had evaluable ADA data. If there were no data after the date of randomization, the endpoint was considered missing.

The number of participants with postbaseline detection of treatment-emergent antidrug LY2189265 antibodies (ADA) is summarized.

Outcome measures

Outcome measures
Measure	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=698 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Antibodies to LY2189265	—	9 participants	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline through 104 weeks

Population: All randomized participants.

The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively. 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	Sitagliptin n=304 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=15 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=30 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=10 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 n=25 Participants LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 n=24 Participants LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) n=177 Participants Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) n=177 Participants Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Number of Participants With Adjudicated Pancreatitis at 104 Weeks	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants	0 participants	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline through 104 weeks

Population: All randomized participants.

Data on any new cardiovascular (CV) event was prospectively collected using a CV event electronic case report form. At prespecified visits, participants were asked about any new CV event. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs to be adjudicated include myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with adjudicated CV events is summarized cumulatively. 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	Sitagliptin n=304 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.5 mg LY2189265 n=15 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.75 mg LY2189265 n=30 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=10 Participants LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 n=302 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	0.5 mg LY2189265 n=25 Participants LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 n=24 Participants LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin n=315 Participants Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 26 Weeks) n=177 Participants Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (26 Weeks Through 104 Weeks) n=177 Participants Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Number of Participants With Adjudicated Cardiovascular Events at 104 Weeks Participants With Any CV Event	6 participants	0 participants	0 participants	0 participants	4 participants	0 participants	0 participants	5 participants	0 participants	3 participants
Number of Participants With Adjudicated Cardiovascular Events at 104 Weeks Participants With a Fatal CV Event	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	1 participants
Number of Participants With Adjudicated Cardiovascular Events at 104 Weeks Participants With a Non-fatal CV Event	6 participants	0 participants	0 participants	0 participants	4 participants	0 participants	0 participants	4 participants	0 participants	2 participants

Adverse Events

3.0 mg LY2189265

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

2.0 mg LY2189265

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

1.5 mg LY2189265

Serious events: 36 serious events

Other events: 252 other events

Deaths: 0 deaths

1.0 mg LY2189265

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

0.75 mg LY2189265

Serious events: 23 serious events

Other events: 255 other events

Deaths: 0 deaths

0.5 mg LY2189265

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

0.25 mg LY2189265

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Sitagliptin

Serious events: 32 serious events

Other events: 239 other events

Deaths: 0 deaths

Placebo/Sitagliptin (Baseline Through 104 Weeks)

Serious events: 17 serious events

Other events: 138 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	3.0 mg LY2189265 n=15 participants at risk LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)	2.0 mg LY2189265 n=30 participants at risk LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)	1.5 mg LY2189265 n=304 participants at risk LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=10 participants at risk LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 n=302 participants at risk LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally, for 104 weeks	0.5 mg LY2189265 n=25 participants at risk LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 n=24 participants at risk LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin n=315 participants at risk Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 104 Weeks) n=177 participants at risk Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily, for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Blood and lymphatic system disorders Anaemia	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Cardiac disorders Acute myocardial infarction	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Cardiac disorders Angina pectoris	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Cardiac disorders Angina unstable	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Cardiac disorders Atrial fibrillation	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Cardiac disorders Cardio-respiratory arrest	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Cardiac disorders Coronary artery disease	0.00% 0/15	0.00% 0/30	0.66% 2/304 • Number of events 2	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Cardiac disorders Coronary artery stenosis	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Cardiac disorders Mitral valve incompetence	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Cardiac disorders Myocardial infarction	0.00% 0/15	0.00% 0/30	0.66% 2/304 • Number of events 2	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	1.1% 2/177 • Number of events 2
Cardiac disorders Myocardial ischaemia	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Cardiac disorders Prinzmetal angina	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Cardiac disorders Supraventricular tachycardia	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Ear and labyrinth disorders Vertigo	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Endocrine disorders Goitre	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Eye disorders Cataract	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.56% 1/177 • Number of events 1
Eye disorders Retinal detachment	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Eye disorders Retinal vein thrombosis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Gastrointestinal disorders Abdominal hernia	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Gastrointestinal disorders Femoral hernia, obstructive	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Gastrointestinal disorders Gastritis	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Gastrointestinal disorders Haematemesis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Gastrointestinal disorders Hiatus hernia	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Gastrointestinal disorders Intestinal obstruction	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Gastrointestinal disorders Oesophageal varices haemorrhage	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 2	0.00% 0/177
Gastrointestinal disorders Pancreatitis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Gastrointestinal disorders Pancreatitis acute	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Gastrointestinal disorders Umbilical hernia	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
General disorders Chest pain	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.63% 2/315 • Number of events 2	0.00% 0/177
General disorders Injection site nodule	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
General disorders Non-cardiac chest pain	0.00% 0/15	0.00% 0/30	0.66% 2/304 • Number of events 2	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
General disorders Sudden death	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Hepatobiliary disorders Cholelithiasis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Hepatobiliary disorders Hepatitis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Infections and infestations Appendicitis	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Infections and infestations Cystitis	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Infections and infestations Gastroenteritis	6.7% 1/15 • Number of events 1	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Infections and infestations Injection site infection	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Infections and infestations Kidney infection	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Infections and infestations Localised infection	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Infections and infestations Lung infection	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Infections and infestations Pelvic inflammatory disease	0.00% 0/10	0.00% 0/22	0.63% 1/158 • Number of events 1	0.00% 0/7	0.00% 0/168	0.00% 0/12	0.00% 0/15	0.00% 0/164	0.00% 0/87
Infections and infestations Pneumonia	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	4.0% 1/25 • Number of events 1	0.00% 0/24	0.63% 2/315 • Number of events 3	0.00% 0/177
Infections and infestations Pyelonephritis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Infections and infestations Pyelonephritis acute	0.00% 0/15	0.00% 0/30	0.66% 2/304 • Number of events 2	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Infections and infestations Septic shock	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Infections and infestations Tubo-ovarian abscess	0.00% 0/10	0.00% 0/22	0.63% 1/158 • Number of events 1	0.00% 0/7	0.00% 0/168	0.00% 0/12	0.00% 0/15	0.00% 0/164	0.00% 0/87
Infections and infestations Urinary tract infection	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.66% 2/302 • Number of events 2	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Infections and infestations Urosepsis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Injury, poisoning and procedural complications Brain contusion	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Injury, poisoning and procedural complications Epicondylitis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Injury, poisoning and procedural complications Fall	0.00% 0/15	0.00% 0/30	0.66% 2/304 • Number of events 2	0.00% 0/10	0.66% 2/302 • Number of events 2	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Injury, poisoning and procedural complications Forearm fracture	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Injury, poisoning and procedural complications Head injury	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Injury, poisoning and procedural complications Intervertebral disc injury	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Injury, poisoning and procedural complications Limb injury	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Injury, poisoning and procedural complications Meniscus lesion	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Injury, poisoning and procedural complications Radius fracture	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Injury, poisoning and procedural complications Skull fracture	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Investigations Blood calcitonin increased	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.99% 3/302 • Number of events 3	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Musculoskeletal and connective tissue disorders Exostosis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Musculoskeletal and connective tissue disorders Myofascial pain syndrome	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Musculoskeletal and connective tissue disorders Myopathy	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.56% 1/177 • Number of events 1
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer stage iii	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-secretory adenoma of pituitary	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal adenocarcinoma	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/5	0.00% 0/8	0.00% 0/146	0.00% 0/3	0.00% 0/134	0.00% 0/13	0.00% 0/9	0.66% 1/151 • Number of events 1	0.00% 0/90
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenoma	0.00% 0/5	0.00% 0/8	0.68% 1/146 • Number of events 1	0.00% 0/3	0.75% 1/134 • Number of events 1	0.00% 0/13	0.00% 0/9	0.00% 0/151	0.00% 0/90
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/15	3.3% 1/30 • Number of events 1	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/10	0.00% 0/22	0.00% 0/158	0.00% 0/7	0.00% 0/168	0.00% 0/12	0.00% 0/15	0.61% 1/164 • Number of events 1	0.00% 0/87
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/10	0.00% 0/22	0.63% 1/158 • Number of events 1	0.00% 0/7	0.00% 0/168	0.00% 0/12	0.00% 0/15	0.00% 0/164	0.00% 0/87
Nervous system disorders Cerebrovascular accident	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Nervous system disorders Coma	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Nervous system disorders Demyelinating polyneuropathy	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Nervous system disorders Epilepsy	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Nervous system disorders Intracranial aneurysm	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Nervous system disorders Ischaemic stroke	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Renal and urinary disorders Calculus ureteric	0.00% 0/15	0.00% 0/30	0.66% 2/304 • Number of events 2	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Renal and urinary disorders Calculus urinary	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Renal and urinary disorders Haematuria	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Renal and urinary disorders Nephritis	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Renal and urinary disorders Nephrolithiasis	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Renal and urinary disorders Urinary retention	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 2	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Reproductive system and breast disorders Cervical dysplasia	0.00% 0/10	0.00% 0/22	0.00% 0/158	0.00% 0/7	0.00% 0/168	0.00% 0/12	0.00% 0/15	0.00% 0/164	1.1% 1/87 • Number of events 1
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 2	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Skin and subcutaneous tissue disorders Diabetic foot	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Skin and subcutaneous tissue disorders Stevens-johnson syndrome	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Surgical and medical procedures Cholecystectomy	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Surgical and medical procedures Spinal operation	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Vascular disorders Deep vein thrombosis	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Vascular disorders Haematoma	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1
Vascular disorders Hypertension	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.66% 2/302 • Number of events 2	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Vascular disorders Varicose vein	0.00% 0/15	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1

Other adverse events

Other adverse events
Measure	3.0 mg LY2189265 n=15 participants at risk LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)	2.0 mg LY2189265 n=30 participants at risk LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)	1.5 mg LY2189265 n=304 participants at risk LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	1.0 mg LY2189265 n=10 participants at risk LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	0.75 mg LY2189265 n=302 participants at risk LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally, for 104 weeks	0.5 mg LY2189265 n=25 participants at risk LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)	0.25 mg LY2189265 n=24 participants at risk LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks) Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks) Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)	Sitagliptin n=315 participants at risk Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks	Placebo/Sitagliptin (Baseline Through 104 Weeks) n=177 participants at risk Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks Placebo: tablet, administered orally, once daily for 26 weeks Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily, for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks
Eye disorders Visual acuity reduced	0.00% 0/15	0.00% 0/30	0.33% 1/304 • Number of events 1	10.0% 1/10 • Number of events 1	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Gastrointestinal disorders Abdominal discomfort	0.00% 0/15	10.0% 3/30 • Number of events 3	3.3% 10/304 • Number of events 17	0.00% 0/10	0.99% 3/302 • Number of events 4	0.00% 0/25	4.2% 1/24 • Number of events 1	2.2% 7/315 • Number of events 7	0.56% 1/177 • Number of events 1
Gastrointestinal disorders Abdominal distension	0.00% 0/15	0.00% 0/30	4.3% 13/304 • Number of events 14	10.0% 1/10 • Number of events 1	5.0% 15/302 • Number of events 18	8.0% 2/25 • Number of events 2	0.00% 0/24	0.95% 3/315 • Number of events 3	0.56% 1/177 • Number of events 1
Gastrointestinal disorders Abdominal pain	6.7% 1/15 • Number of events 1	0.00% 0/30	6.9% 21/304 • Number of events 26	0.00% 0/10	4.3% 13/302 • Number of events 24	4.0% 1/25 • Number of events 1	0.00% 0/24	3.5% 11/315 • Number of events 12	2.3% 4/177 • Number of events 6
Gastrointestinal disorders Abdominal pain upper	0.00% 0/15	3.3% 1/30 • Number of events 1	4.6% 14/304 • Number of events 15	0.00% 0/10	4.0% 12/302 • Number of events 13	4.0% 1/25 • Number of events 1	0.00% 0/24	2.9% 9/315 • Number of events 10	5.6% 10/177 • Number of events 12
Gastrointestinal disorders Constipation	6.7% 1/15 • Number of events 1	0.00% 0/30	4.6% 14/304 • Number of events 14	0.00% 0/10	5.3% 16/302 • Number of events 22	12.0% 3/25 • Number of events 3	0.00% 0/24	1.3% 4/315 • Number of events 4	0.56% 1/177 • Number of events 1
Gastrointestinal disorders Diarrhoea	0.00% 0/15	16.7% 5/30 • Number of events 5	16.4% 50/304 • Number of events 74	10.0% 1/10 • Number of events 1	11.9% 36/302 • Number of events 53	16.0% 4/25 • Number of events 5	8.3% 2/24 • Number of events 2	5.7% 18/315 • Number of events 30	8.5% 15/177 • Number of events 23
Gastrointestinal disorders Dyspepsia	0.00% 0/15	3.3% 1/30 • Number of events 1	5.9% 18/304 • Number of events 25	10.0% 1/10 • Number of events 1	6.3% 19/302 • Number of events 23	12.0% 3/25 • Number of events 4	4.2% 1/24 • Number of events 1	5.1% 16/315 • Number of events 17	2.3% 4/177 • Number of events 4
Gastrointestinal disorders Eructation	0.00% 0/15	6.7% 2/30 • Number of events 2	1.3% 4/304 • Number of events 9	0.00% 0/10	0.33% 1/302 • Number of events 1	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Gastrointestinal disorders Flatulence	6.7% 1/15 • Number of events 1	6.7% 2/30 • Number of events 2	2.3% 7/304 • Number of events 9	0.00% 0/10	1.7% 5/302 • Number of events 6	0.00% 0/25	0.00% 0/24	0.95% 3/315 • Number of events 3	0.56% 1/177 • Number of events 1
Gastrointestinal disorders Gastritis	0.00% 0/15	3.3% 1/30 • Number of events 1	3.6% 11/304 • Number of events 12	20.0% 2/10 • Number of events 3	1.3% 4/302 • Number of events 4	0.00% 0/25	0.00% 0/24	2.9% 9/315 • Number of events 9	4.0% 7/177 • Number of events 8
Gastrointestinal disorders Gastrooesophageal reflux disease	6.7% 1/15 • Number of events 1	3.3% 1/30 • Number of events 1	2.3% 7/304 • Number of events 8	0.00% 0/10	2.6% 8/302 • Number of events 8	0.00% 0/25	0.00% 0/24	2.2% 7/315 • Number of events 7	1.7% 3/177 • Number of events 4
Gastrointestinal disorders Nausea	33.3% 5/15 • Number of events 6	20.0% 6/30 • Number of events 6	17.4% 53/304 • Number of events 98	40.0% 4/10 • Number of events 5	14.6% 44/302 • Number of events 62	12.0% 3/25 • Number of events 6	8.3% 2/24 • Number of events 3	7.0% 22/315 • Number of events 27	5.1% 9/177 • Number of events 15
Gastrointestinal disorders Vomiting	13.3% 2/15 • Number of events 2	13.3% 4/30 • Number of events 6	13.5% 41/304 • Number of events 62	20.0% 2/10 • Number of events 2	8.3% 25/302 • Number of events 43	4.0% 1/25 • Number of events 1	4.2% 1/24 • Number of events 2	3.5% 11/315 • Number of events 11	1.7% 3/177 • Number of events 3
General disorders Asthenia	0.00% 0/15	6.7% 2/30 • Number of events 3	2.3% 7/304 • Number of events 8	0.00% 0/10	2.0% 6/302 • Number of events 6	0.00% 0/25	0.00% 0/24	1.6% 5/315 • Number of events 5	1.1% 2/177 • Number of events 2
General disorders Chills	0.00% 0/15	0.00% 0/30	0.00% 0/304	10.0% 1/10 • Number of events 1	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
General disorders Fatigue	0.00% 0/15	0.00% 0/30	4.3% 13/304 • Number of events 15	10.0% 1/10 • Number of events 1	3.0% 9/302 • Number of events 9	0.00% 0/25	8.3% 2/24 • Number of events 2	3.5% 11/315 • Number of events 11	3.4% 6/177 • Number of events 6
General disorders Temperature intolerance	0.00% 0/15	0.00% 0/30	0.00% 0/304	10.0% 1/10 • Number of events 1	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Infections and infestations Gastroenteritis	13.3% 2/15 • Number of events 2	0.00% 0/30	3.9% 12/304 • Number of events 12	0.00% 0/10	2.3% 7/302 • Number of events 10	4.0% 1/25 • Number of events 1	0.00% 0/24	1.9% 6/315 • Number of events 6	4.0% 7/177 • Number of events 8
Infections and infestations Influenza	0.00% 0/15	3.3% 1/30 • Number of events 2	5.3% 16/304 • Number of events 19	0.00% 0/10	6.0% 18/302 • Number of events 22	0.00% 0/25	0.00% 0/24	4.4% 14/315 • Number of events 15	2.8% 5/177 • Number of events 5
Infections and infestations Nasopharyngitis	0.00% 0/15	3.3% 1/30 • Number of events 1	14.1% 43/304 • Number of events 64	0.00% 0/10	15.9% 48/302 • Number of events 96	4.0% 1/25 • Number of events 1	0.00% 0/24	14.9% 47/315 • Number of events 72	14.1% 25/177 • Number of events 44
Infections and infestations Sinusitis	0.00% 0/15	3.3% 1/30 • Number of events 1	4.9% 15/304 • Number of events 22	0.00% 0/10	3.3% 10/302 • Number of events 14	8.0% 2/25 • Number of events 2	0.00% 0/24	2.2% 7/315 • Number of events 7	1.7% 3/177 • Number of events 3
Infections and infestations Upper respiratory tract infection	6.7% 1/15 • Number of events 1	0.00% 0/30	7.2% 22/304 • Number of events 34	0.00% 0/10	7.3% 22/302 • Number of events 30	4.0% 1/25 • Number of events 1	0.00% 0/24	6.7% 21/315 • Number of events 24	4.0% 7/177 • Number of events 8
Infections and infestations Urinary tract infection	0.00% 0/15	6.7% 2/30 • Number of events 2	6.9% 21/304 • Number of events 26	0.00% 0/10	7.0% 21/302 • Number of events 25	4.0% 1/25 • Number of events 1	4.2% 1/24 • Number of events 1	6.0% 19/315 • Number of events 22	7.9% 14/177 • Number of events 21
Investigations Amylase increased	0.00% 0/15	0.00% 0/30	2.0% 6/304 • Number of events 11	10.0% 1/10 • Number of events 1	1.7% 5/302 • Number of events 9	4.0% 1/25 • Number of events 1	0.00% 0/24	1.9% 6/315 • Number of events 8	0.56% 1/177 • Number of events 1
Investigations Blood calcitonin increased	0.00% 0/15	0.00% 0/30	0.66% 2/304 • Number of events 2	10.0% 1/10 • Number of events 1	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.63% 2/315 • Number of events 3	0.56% 1/177 • Number of events 2
Investigations Lipase increased	0.00% 0/15	0.00% 0/30	3.6% 11/304 • Number of events 14	0.00% 0/10	4.3% 13/302 • Number of events 21	8.0% 2/25 • Number of events 2	4.2% 1/24 • Number of events 1	4.8% 15/315 • Number of events 16	2.8% 5/177 • Number of events 9
Metabolism and nutrition disorders Decreased appetite	0.00% 0/15	10.0% 3/30 • Number of events 5	9.5% 29/304 • Number of events 31	10.0% 1/10 • Number of events 1	5.6% 17/302 • Number of events 23	8.0% 2/25 • Number of events 2	4.2% 1/24 • Number of events 1	3.5% 11/315 • Number of events 11	1.7% 3/177 • Number of events 3
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/15	0.00% 0/30	9.9% 30/304 • Number of events 30	0.00% 0/10	12.6% 38/302 • Number of events 38	0.00% 0/25	0.00% 0/24	15.6% 49/315 • Number of events 49	15.8% 28/177 • Number of events 28
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/15	0.00% 0/30	4.9% 15/304 • Number of events 19	0.00% 0/10	6.3% 19/302 • Number of events 22	0.00% 0/25	0.00% 0/24	4.4% 14/315 • Number of events 16	4.0% 7/177 • Number of events 11
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/15	0.00% 0/30	6.9% 21/304 • Number of events 28	0.00% 0/10	9.3% 28/302 • Number of events 32	8.0% 2/25 • Number of events 2	0.00% 0/24	6.0% 19/315 • Number of events 24	5.1% 9/177 • Number of events 9
Musculoskeletal and connective tissue disorders Synovial cyst	0.00% 0/15	0.00% 0/30	0.00% 0/304	10.0% 1/10 • Number of events 1	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.00% 0/177
Nervous system disorders Dizziness	6.7% 1/15 • Number of events 1	6.7% 2/30 • Number of events 3	2.3% 7/304 • Number of events 8	0.00% 0/10	6.0% 18/302 • Number of events 20	0.00% 0/25	0.00% 0/24	4.4% 14/315 • Number of events 20	3.4% 6/177 • Number of events 6
Nervous system disorders Headache	0.00% 0/15	3.3% 1/30 • Number of events 1	9.5% 29/304 • Number of events 53	0.00% 0/10	8.9% 27/302 • Number of events 76	4.0% 1/25 • Number of events 1	4.2% 1/24 • Number of events 3	8.3% 26/315 • Number of events 33	6.8% 12/177 • Number of events 17
Psychiatric disorders Depression	0.00% 0/15	0.00% 0/30	2.3% 7/304 • Number of events 7	10.0% 1/10 • Number of events 1	1.3% 4/302 • Number of events 4	4.0% 1/25 • Number of events 1	0.00% 0/24	1.6% 5/315 • Number of events 5	0.56% 1/177 • Number of events 1
Psychiatric disorders Insomnia	0.00% 0/15	0.00% 0/30	2.3% 7/304 • Number of events 10	0.00% 0/10	1.3% 4/302 • Number of events 4	8.0% 2/25 • Number of events 2	0.00% 0/24	2.2% 7/315 • Number of events 8	1.1% 2/177 • Number of events 2
Respiratory, thoracic and mediastinal disorders Asthma	6.7% 1/15 • Number of events 1	0.00% 0/30	1.3% 4/304 • Number of events 4	0.00% 0/10	1.7% 5/302 • Number of events 6	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.00% 0/177
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/15	0.00% 0/30	6.2% 19/304 • Number of events 24	0.00% 0/10	3.6% 11/302 • Number of events 12	0.00% 0/25	0.00% 0/24	5.4% 17/315 • Number of events 26	3.4% 6/177 • Number of events 7
Skin and subcutaneous tissue disorders Ingrowing nail	0.00% 0/15	0.00% 0/30	0.00% 0/304	10.0% 1/10 • Number of events 1	0.66% 2/302 • Number of events 3	0.00% 0/25	4.2% 1/24 • Number of events 1	0.00% 0/315	0.56% 1/177 • Number of events 1
Vascular disorders Hypotension	6.7% 1/15 • Number of events 1	0.00% 0/30	0.00% 0/304	0.00% 0/10	0.99% 3/302 • Number of events 4	0.00% 0/25	0.00% 0/24	0.32% 1/315 • Number of events 1	0.56% 1/177 • Number of events 1
Vascular disorders Venous insufficiency	6.7% 1/15 • Number of events 1	0.00% 0/30	0.33% 1/304 • Number of events 1	0.00% 0/10	0.00% 0/302	0.00% 0/25	0.00% 0/24	0.00% 0/315	0.56% 1/177 • Number of events 1

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