Trial Outcomes & Findings for A Study in Participants With Type 2 Diabetes Mellitus (AWARD-4) (NCT NCT01191268)

NCT ID: NCT01191268

Last Updated: 2014-10-08

Results Overview

Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

884 participants

Primary outcome timeframe

Baseline, 26 weeks

Results posted on

2014-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	1.5 mg LY2189265 LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	Insulin Glargine Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Overall Study STARTED	295	293	296
Overall Study Received at Least One Dose of Study Drug	295	293	296
Overall Study COMPLETED	237	238	244
Overall Study NOT COMPLETED	58	55	52

Reasons for withdrawal

Reasons for withdrawal
Measure	1.5 mg LY2189265 LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	Insulin Glargine Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Overall Study Withdrawal by Subject	19	25	21
Overall Study Adverse Event	21	13	8
Overall Study Physician Decision	6	8	9
Overall Study Lost to Follow-up	8	5	9
Overall Study Entry Criteria Not Met	3	1	1
Overall Study Death	0	1	3
Overall Study Protocol Violation	1	0	1
Overall Study Sponsor Decision	0	2	0

Baseline Characteristics

A Study in Participants With Type 2 Diabetes Mellitus (AWARD-4)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	Total n=884 Participants Total of all reporting groups
Age, Continuous	58.88 years STANDARD_DEVIATION 9.55 • n=93 Participants	59.31 years STANDARD_DEVIATION 8.98 • n=4 Participants	59.90 years STANDARD_DEVIATION 9.08 • n=27 Participants	59.36 years STANDARD_DEVIATION 9.21 • n=483 Participants
Sex: Female, Male Female	135 Participants n=93 Participants	145 Participants n=4 Participants	131 Participants n=27 Participants	411 Participants n=483 Participants
Sex: Female, Male Male	160 Participants n=93 Participants	148 Participants n=4 Participants	165 Participants n=27 Participants	473 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	102 Participants n=93 Participants	101 Participants n=4 Participants	100 Participants n=27 Participants	303 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	193 Participants n=93 Participants	192 Participants n=4 Participants	196 Participants n=27 Participants	581 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	16 Participants n=93 Participants	13 Participants n=4 Participants	17 Participants n=27 Participants	46 Participants n=483 Participants
Race (NIH/OMB) Asian	9 Participants n=93 Participants	12 Participants n=4 Participants	14 Participants n=27 Participants	35 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Black or African American	32 Participants n=93 Participants	27 Participants n=4 Participants	26 Participants n=27 Participants	85 Participants n=483 Participants
Race (NIH/OMB) White	231 Participants n=93 Participants	235 Participants n=4 Participants	231 Participants n=27 Participants	697 Participants n=483 Participants
Race (NIH/OMB) More than one race	7 Participants n=93 Participants	6 Participants n=4 Participants	7 Participants n=27 Participants	20 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Region of Enrollment United States	103 participants n=93 Participants	95 participants n=4 Participants	96 participants n=27 Participants	294 participants n=483 Participants
Region of Enrollment Taiwan	8 participants n=93 Participants	9 participants n=4 Participants	9 participants n=27 Participants	26 participants n=483 Participants
Region of Enrollment Greece	8 participants n=93 Participants	7 participants n=4 Participants	8 participants n=27 Participants	23 participants n=483 Participants
Region of Enrollment Spain	8 participants n=93 Participants	10 participants n=4 Participants	9 participants n=27 Participants	27 participants n=483 Participants
Region of Enrollment Russian Federation	6 participants n=93 Participants	8 participants n=4 Participants	9 participants n=27 Participants	23 participants n=483 Participants
Region of Enrollment Hungary	19 participants n=93 Participants	19 participants n=4 Participants	19 participants n=27 Participants	57 participants n=483 Participants
Region of Enrollment Mexico	19 participants n=93 Participants	19 participants n=4 Participants	17 participants n=27 Participants	55 participants n=483 Participants
Region of Enrollment Canada	9 participants n=93 Participants	8 participants n=4 Participants	9 participants n=27 Participants	26 participants n=483 Participants
Region of Enrollment Puerto Rico	13 participants n=93 Participants	20 participants n=4 Participants	18 participants n=27 Participants	51 participants n=483 Participants
Region of Enrollment Argentina	26 participants n=93 Participants	27 participants n=4 Participants	28 participants n=27 Participants	81 participants n=483 Participants
Region of Enrollment Poland	13 participants n=93 Participants	13 participants n=4 Participants	14 participants n=27 Participants	40 participants n=483 Participants
Region of Enrollment Brazil	33 participants n=93 Participants	30 participants n=4 Participants	32 participants n=27 Participants	95 participants n=483 Participants
Region of Enrollment Belgium	5 participants n=93 Participants	5 participants n=4 Participants	4 participants n=27 Participants	14 participants n=483 Participants
Region of Enrollment Denmark	4 participants n=93 Participants	4 participants n=4 Participants	4 participants n=27 Participants	12 participants n=483 Participants
Region of Enrollment Australia	10 participants n=93 Participants	8 participants n=4 Participants	8 participants n=27 Participants	26 participants n=483 Participants
Region of Enrollment Sweden	11 participants n=93 Participants	11 participants n=4 Participants	12 participants n=27 Participants	34 participants n=483 Participants
Body Weight	91.00 kilograms (kg) STANDARD_DEVIATION 18.24 • n=93 Participants	91.69 kilograms (kg) STANDARD_DEVIATION 18.03 • n=4 Participants	90.75 kilograms (kg) STANDARD_DEVIATION 18.87 • n=27 Participants	91.14 kilograms (kg) STANDARD_DEVIATION 18.37 • n=483 Participants
Body Mass Index (BMI)	31.99 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.11 • n=93 Participants	33.08 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.15 • n=4 Participants	32.41 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.33 • n=27 Participants	32.49 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.21 • n=483 Participants
Glycosylated Hemoglobin (HbA1c)	8.46 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.08 • n=93 Participants	8.40 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.03 • n=4 Participants	8.53 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.03 • n=27 Participants	8.46 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.05 • n=483 Participants
Duration of Diabetes	12.80 years STANDARD_DEVIATION 7.19 • n=93 Participants	12.43 years STANDARD_DEVIATION 6.92 • n=4 Participants	12.96 years STANDARD_DEVIATION 6.80 • n=27 Participants	12.73 years STANDARD_DEVIATION 6.97 • n=483 Participants

PRIMARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable HbA1c data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=276 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=275 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)	-1.41 percentage of glycosylated hemoglobin Standard Error 0.07	-1.64 percentage of glycosylated hemoglobin Standard Error 0.07	-1.59 percentage of glycosylated hemoglobin Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=276 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=275 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)	-1.23 percentage of glycosylated hemoglobin Standard Error 0.08	-1.48 percentage of glycosylated hemoglobin Standard Error 0.08	-1.42 percentage of glycosylated hemoglobin Standard Error 0.08

SECONDARY outcome

Timeframe: 26 weeks and 52 weeks

The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a repeated logistic regression model (generalized estimating equation model) with baseline HbA1c, baseline metformin, country, and treatment as factors included in the model.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=280 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=275 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=277 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 HbA1c less than or equal to 6.5%, 52 weeks	30.4 percentage of participants	36.7 percentage of participants	34.7 percentage of participants
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 HbA1c less than 7.0%, 26 weeks	56.8 percentage of participants	67.6 percentage of participants	69.0 percentage of participants
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 HbA1c less than 7.0%, 52 weeks	49.3 percentage of participants	58.5 percentage of participants	56.3 percentage of participants
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 HbA1c less than or equal to 6.5%, 26 weeks	37.5 percentage of participants	48.0 percentage of participants	43.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

The percentage of participants achieving HbA1c less than 7.0% without nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking) or severe (episodes requiring the assistance of another person to actively administer resuscitative actions) hypoglycemia was analyzed with a repeated logistic regression model (generalized estimating equation model) with baseline HbA1c, baseline metformin, country, and treatment as factors included in the model.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=280 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=275 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=277 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia 26 weeks	28.2 percentage of participants	53.8 percentage of participants	54.5 percentage of participants
Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia 52 weeks	26.8 percentage of participants	44.0 percentage of participants	44.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable SMPG data. Only pre-rescue measurements were used.

The self-monitored plasma glucose (SMPG) data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. The mean of the 8 time points (Daily Mean) was also calculated. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, metformin, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable fasting blood glucose data. Only pre-rescue measurements were used.

Fasting serum glucose was measured by the central laboratory. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline fasting blood glucose as a covariate.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=294 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=292 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose 26 weeks (n=253, 256, 255)	-1.58 millimoles per liter (mmol/L) Standard Error 0.20	-0.27 millimoles per liter (mmol/L) Standard Error 0.20	0.22 millimoles per liter (mmol/L) Standard Error 0.20
Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose 52 weeks (n=237, 238, 246)	-1.01 millimoles per liter (mmol/L) Standard Error 0.22	0.08 millimoles per liter (mmol/L) Standard Error 0.22	0.41 millimoles per liter (mmol/L) Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline and 26 weeks and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.

Total daily insulin (TDI) dose was reported at baseline, 26 weeks, and 52 weeks. Daily Insulin Lispro and Insulin Glargine doses were reported at 26 and 52 weeks.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) TDI, 26 weeks (n=244, 251, 254)	132.00 units Standard Deviation 79.01	93.24 units Standard Deviation 78.02	96.69 units Standard Deviation 62.13
Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) TDI, 52 weeks (n=224, 227, 238)	133.19 units Standard Deviation 80.75	88.15 units Standard Deviation 62.95	95.00 units Standard Deviation 67.62
Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) TDI, Baseline	53.93 units Standard Deviation 30.67	55.20 units Standard Deviation 32.17	59.11 units Standard Deviation 38.12
Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) Insulin Lispro, 26 weeks (n=244, 251, 254)	67.79 units Standard Deviation 44.59	93.24 units Standard Deviation 78.02	96.69 units Standard Deviation 62.13
Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) Insulin Lispro, 52 weeks (n=224, 227, 238)	69.12 units Standard Deviation 49.07	88.15 units Standard Deviation 62.95	95.00 units Standard Deviation 67.62
Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) Insulin Glargine, 26 weeks (n=244, 251, 254)	64.48 units Standard Deviation 40.23	NA units Standard Deviation NA Participants in this treatment arm were not exposed to Insulin Glargine.	NA units Standard Deviation NA Participants in this treatment arm were not exposed to Insulin Glargine.
Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) Insulin Glargine, 52 weeks (n=224, 227, 238)	64.07 units Standard Deviation 38.60	NA units Standard Deviation NA Participants in this treatment arm were not exposed to Insulin Glargine.	NA units Standard Deviation NA Participants in this treatment arm were not exposed to Insulin Glargine.

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable body weight data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment, and metformin use as fixed effects and baseline body weight as a covariate.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=294 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=286 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=289 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in Body Weight 26 weeks	2.33 kilograms (kg) Standard Error 0.27	-0.87 kilograms (kg) Standard Error 0.27	0.18 kilograms (kg) Standard Error 0.27
Change From Baseline to 26 and 52 Weeks in Body Weight 52 weeks	2.89 kilograms (kg) Standard Error 0.33	-0.35 kilograms (kg) Standard Error 0.34	0.86 kilograms (kg) Standard Error 0.33

SECONDARY outcome

Timeframe: Baseline and 52 weeks and 4 weeks after last dose

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable body weight data.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose 52 weeks (n=290, 290, 295)	94.14 kilograms (kg) Standard Deviation 19.72	91.58 kilograms (kg) Standard Deviation 19.06	93.21 kilograms (kg) Standard Deviation 19.23
Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose Baseline	90.75 kilograms (kg) Standard Deviation 18.87	91.00 kilograms (kg) Standard Deviation 18.24	91.69 kilograms (kg) Standard Deviation 18.03
Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose 4 weeks after last dose (n=259, 260, 253)	94.27 kilograms (kg) Standard Deviation 20.13	91.69 kilograms (kg) Standard Deviation 18.60	93.14 kilograms (kg) Standard Deviation 19.20

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable BMI data.

Body mass index is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline BMI as a covariate.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) 26 weeks (n=248, 251, 250)	1.01 kilograms per meter squared (kg/m^2) Standard Error 0.09	-0.20 kilograms per meter squared (kg/m^2) Standard Error 0.09	0.21 kilograms per meter squared (kg/m^2) Standard Error 0.09
Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) 52 weeks (n=225, 224, 232)	1.33 kilograms per meter squared (kg/m^2) Standard Error 0.11	0.09 kilograms per meter squared (kg/m^2) Standard Error 0.11	0.57 kilograms per meter squared (kg/m^2) Standard Error 0.11
Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) 4 weeks after last dose	NA kilograms per meter squared (kg/m^2) Standard Error NA Data from 4 weeks after last dose was not analyzed for this outcome.	NA kilograms per meter squared (kg/m^2) Standard Error NA Data from 4 weeks after last dose was not analyzed for this outcome.	NA kilograms per meter squared (kg/m^2) Standard Error NA Data from 4 weeks after last dose was not analyzed for this outcome.

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable EQ-5D data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

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

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in the EQ-5D EQ-5D UK, 26 weeks (n=272, 271, 274)	-0.03 units on a scale Standard Error 0.01	-0.03 units on a scale Standard Error 0.01	-0.03 units on a scale Standard Error 0.01
Change From Baseline to 26 and 52 Weeks in the EQ-5D EQ-5D UK, 52 weeks (n=274, 274, 281)	-0.03 units on a scale Standard Error 0.01	-0.04 units on a scale Standard Error 0.01	-0.04 units on a scale Standard Error 0.01
Change From Baseline to 26 and 52 Weeks in the EQ-5D VAS, 26 weeks (n=278, 275, 275)	-0.60 units on a scale Standard Error 1.00	-1.69 units on a scale Standard Error 1.00	-2.30 units on a scale Standard Error 1.00
Change From Baseline to 26 and 52 Weeks in the EQ-5D VAS, 52 weeks (n=279, 278, 282)	-0.18 units on a scale Standard Error 1.01	-0.46 units on a scale Standard Error 1.01	-2.54 units on a scale Standard Error 1.02

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable APPADL data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

The Impact of Weight on Activities of Daily Living questionnaire (renamed the Ability to Perform Physical Activities of Daily Living Questionnaire \[APPADL\]) contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = "not at all difficult" and 1 = "unable to do". The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment, and metformin use as fixed effects and baseline score as a covariate.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=294 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=290 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) 26 weeks (n=274, 270, 270)	-0.93 units on a scale Standard Error 0.31	-0.50 units on a scale Standard Error 0.30	-0.60 units on a scale Standard Error 0.31
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) 52 weeks (n=277, 275, 279)	-1.28 units on a scale Standard Error 0.33	-0.50 units on a scale Standard Error 0.33	-1.05 units on a scale Standard Error 0.33

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable IW-SP data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment, and metformin use as fixed effects and baseline score as a covariate.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=295 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=291 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) 26 weeks (n=277, 274, 274)	0.18 units on a scale Standard Error 0.17	0.60 units on a scale Standard Error 0.17	0.34 units on a scale Standard Error 0.17
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) 52 weeks (n=278, 277, 281)	0.06 units on a scale Standard Error 0.16	0.86 units on a scale Standard Error 0.16	0.22 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable LBSS data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

The Low Blood Sugar Survey (LBSS) contains 33 items comprised of 2 subscales (behavior and worry), each of which is rated on a 5-point numeric rating scale from 0 (never) to 4 (almost always). It captures behavioral changes associated with the concerns and experiences of hypoglycemia and the degree to which participants are worried about certain aspects associated with hypoglycemia during the previous 4 weeks. The behavior (or avoidance) subscale has 15 items, and the worry (or affect) subscale has 18 items. Subscale scores are calculated by summing participant responses to items (behavior range 0-60; worry range 0-72). A total score is calculated as the sum of both subscales (range 0-132). Higher scores indicate greater negative impact on subscales and total score. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment and metformin use as fixed effects and baseline score as a covariate.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=292 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS) 26 weeks (n=251, 256, 250)	2.83 units on a scale Standard Error 1.30	3.75 units on a scale Standard Error 1.31	2.91 units on a scale Standard Error 1.29
Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS) 52 weeks (n=234, 238, 244)	2.38 units on a scale Standard Error 1.23	2.51 units on a scale Standard Error 1.25	0.92 units on a scale Standard Error 1.23

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable pancreatic enzyme data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes Amylase (total), 26 weeks (n=284, 282, 287)	1.00 units per liter (U/L) Interval -4.0 to 8.0	5.00 units per liter (U/L) Interval -2.0 to 15.0	4.00 units per liter (U/L) Interval -1.0 to 10.0
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes Amylase (total), 52 weeks (n=284, 283, 287)	0.00 units per liter (U/L) Interval -7.0 to 6.0	2.00 units per liter (U/L) Interval -3.0 to 12.0	2.00 units per liter (U/L) Interval -4.0 to 9.0
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes Amylase (PD), 26 weeks (n=284, 282, 287)	1.00 units per liter (U/L) Interval -2.0 to 4.0	4.00 units per liter (U/L) Interval 0.0 to 10.0	2.50 units per liter (U/L) Interval 0.0 to 7.0
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes Amylase (PD), 52 weeks (n=284, 283, 287)	0.00 units per liter (U/L) Interval -3.0 to 3.0	3.00 units per liter (U/L) Interval -2.0 to 9.0	2.00 units per liter (U/L) Interval -2.0 to 5.0
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes Lipase, 26 weeks (n=284, 282, 287)	-2.00 units per liter (U/L) Interval -8.0 to 3.0	7.00 units per liter (U/L) Interval 0.0 to 17.0	4.00 units per liter (U/L) Interval -3.0 to 12.0
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes Lipase, 52 weeks (n=284, 283, 287)	-2.00 units per liter (U/L) Interval -9.0 to 4.0	6.00 units per liter (U/L) Interval -1.0 to 16.5	3.00 units per liter (U/L) Interval -3.0 to 11.0

SECONDARY outcome

Timeframe: Baseline and 52 weeks and 4 weeks after last dose

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable pancreatic enzyme data.

Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured at baseline and at 4 weeks after last dose (ALD).

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose Amylase (total), Baseline	61.18 units per liter (U/L) Standard Deviation 26.69	61.21 units per liter (U/L) Standard Deviation 27.89	58.59 units per liter (U/L) Standard Deviation 23.19
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose Amylase (total), 52 weeks (n=284, 283, 287)	61.93 units per liter (U/L) Standard Deviation 27.12	66.08 units per liter (U/L) Standard Deviation 30.29	60.97 units per liter (U/L) Standard Deviation 25.78
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose Amylase (total), 4 weeks ALD (n=251, 259, 251)	62.13 units per liter (U/L) Standard Deviation 26.11	61.69 units per liter (U/L) Standard Deviation 28.06	59.21 units per liter (U/L) Standard Deviation 30.32
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose Amylase (PD), Baseline	26.43 units per liter (U/L) Standard Deviation 15.94	26.56 units per liter (U/L) Standard Deviation 14.51	25.10 units per liter (U/L) Standard Deviation 13.48
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose Amylase (PD), 52 weeks (n=284, 283, 287)	26.91 units per liter (U/L) Standard Deviation 17.64	31.38 units per liter (U/L) Standard Deviation 18.15	27.86 units per liter (U/L) Standard Deviation 17.14
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose Amylase (PD), 4 weeks ALD (n=251, 260, 251)	26.84 units per liter (U/L) Standard Deviation 15.44	27.50 units per liter (U/L) Standard Deviation 15.49	25.77 units per liter (U/L) Standard Deviation 13.78
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose Lipase, Baseline	43.20 units per liter (U/L) Standard Deviation 37.35	41.42 units per liter (U/L) Standard Deviation 34.19	41.08 units per liter (U/L) Standard Deviation 32.80
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose Lipase, 52 weeks (n=284, 283, 287)	39.39 units per liter (U/L) Standard Deviation 27.51	50.57 units per liter (U/L) Standard Deviation 35.65	45.34 units per liter (U/L) Standard Deviation 31.23
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose Lipase, 4 weeks ALD (n=252, 260, 251)	43.02 units per liter (U/L) Standard Deviation 35.75	44.19 units per liter (U/L) Standard Deviation 36.92	41.86 units per liter (U/L) Standard Deviation 25.22

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable serum calcitonin data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=294 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in Serum Calcitonin 26 weeks (n=283, 282, 285)	0.00 picogram per milliliter (pcg/mL) Interval 0.0 to 0.0	0.00 picogram per milliliter (pcg/mL) Interval 0.0 to 0.0	0.00 picogram per milliliter (pcg/mL) Interval 0.0 to 0.0
Change From Baseline to 26 and 52 Weeks in Serum Calcitonin 52 weeks (n=283, 283, 285)	0.00 picogram per milliliter (pcg/mL) Interval 0.0 to 0.0	0.00 picogram per milliliter (pcg/mL) Interval 0.0 to 0.0	0.00 picogram per milliliter (pcg/mL) Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline and 52 weeks and 4 weeks after last dose

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable serum calcitonin data.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=294 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose Baseline	0.78 picomole per liter Standard Deviation 0.88	0.75 picomole per liter Standard Deviation 0.78	0.73 picomole per liter Standard Deviation 0.77
Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose 52 weeks (n=284, 283, 285)	0.80 picomole per liter Standard Deviation 0.89	0.79 picomole per liter Standard Deviation 0.89	0.78 picomole per liter Standard Deviation 0.90
Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose 4 weeks after last dose (n=245, 254, 246)	0.87 picomole per liter Standard Deviation 0.95	0.76 picomole per liter Standard Deviation 0.87	0.73 picomole per liter Standard Deviation 0.72

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

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

Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline blood pressure as a covariate.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in Blood Pressure SBP, 26 weeks (n=255, 261, 258)	2.23 milliliters of mercury (mmHg) Standard Error 0.88	-0.97 milliliters of mercury (mmHg) Standard Error 0.88	-0.65 milliliters of mercury (mmHg) Standard Error 0.87
Change From Baseline to 26 and 52 Weeks in Blood Pressure SBP, 52 weeks (n=239, 240, 246)	1.98 milliliters of mercury (mmHg) Standard Error 0.92	-0.26 milliliters of mercury (mmHg) Standard Error 0.94	1.04 milliliters of mercury (mmHg) Standard Error 0.93
Change From Baseline to 26 and 52 Weeks in Blood Pressure DBP, 26 weeks (n=255, 261, 258)	-0.23 milliliters of mercury (mmHg) Standard Error 0.56	0.02 milliliters of mercury (mmHg) Standard Error 0.56	-0.08 milliliters of mercury (mmHg) Standard Error 0.56
Change From Baseline to 26 and 52 Weeks in Blood Pressure DBP, 52 weeks (n=239, 240, 246)	-0.34 milliliters of mercury (mmHg) Standard Error 0.56	-0.01 milliliters of mercury (mmHg) Standard Error 0.57	0.15 milliliters of mercury (mmHg) Standard Error 0.57

SECONDARY outcome

Timeframe: Baseline and 52 weeks and 4 weeks after last dose

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

Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose DBP, Baseline	77.18 milliliters of mercury (mmHg) Standard Deviation 10.41	77.33 milliliters of mercury (mmHg) Standard Deviation 9.73	77.57 milliliters of mercury (mmHg) Standard Deviation 9.00
Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose DBP, 52 weeks (n=290, 290, 295)	77.07 milliliters of mercury (mmHg) Standard Deviation 9.92	77.33 milliliters of mercury (mmHg) Standard Deviation 9.63	77.59 milliliters of mercury (mmHg) Standard Deviation 9.74
Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose SBP, Baseline	133.26 milliliters of mercury (mmHg) Standard Deviation 16.97	133.26 milliliters of mercury (mmHg) Standard Deviation 16.56	134.03 milliliters of mercury (mmHg) Standard Deviation 15.87
Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose SBP, 52 weeks (n=290, 290, 295)	134.90 milliliters of mercury (mmHg) Standard Deviation 16.25	132.67 milliliters of mercury (mmHg) Standard Deviation 15.40	134.31 milliliters of mercury (mmHg) Standard Deviation 16.41
Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose SBP, 4 weeks after last dose (n=260, 260, 255)	132.75 milliliters of mercury (mmHg) Standard Deviation 16.01	133.77 milliliters of mercury (mmHg) Standard Deviation 16.80	134.72 milliliters of mercury (mmHg) Standard Deviation 16.50
Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose DBP, 4 weeks after last dose (n=260, 260, 255)	76.94 milliliters of mercury (mmHg) Standard Deviation 9.10	76.58 milliliters of mercury (mmHg) Standard Deviation 10.06	77.04 milliliters of mercury (mmHg) Standard Deviation 9.60

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable seated pulse rate data.

Seated pulse rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline as a covariate

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in Pulse Rate 26 weeks (n=255, 261, 258)	0.90 beats per minute (bpm) Standard Error 0.56	2.84 beats per minute (bpm) Standard Error 0.57	2.79 beats per minute (bpm) Standard Error 0.56
Change From Baseline to 26 and 52 Weeks in Pulse Rate 52 weeks (n=239, 240, 246)	0.93 beats per minute (bpm) Standard Error 0.57	2.38 beats per minute (bpm) Standard Error 0.57	2.27 beats per minute (bpm) Standard Error 0.57

SECONDARY outcome

Timeframe: Baseline and 52 weeks and 4 weeks after last dose

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable seated pulse rate data.

Seated pulse rate was measured.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose 52 weeks (n=290, 290, 295)	76.02 beats per minute (bpm) Standard Deviation 11.43	78.30 beats per minute (bpm) Standard Deviation 11.01	77.83 beats per minute (bpm) Standard Deviation 10.90
Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose 4 weeks after last dose (n=260, 260, 255)	75.27 beats per minute (bpm) Standard Deviation 11.17	74.52 beats per minute (bpm) Standard Deviation 11.09	74.99 beats per minute (bpm) Standard Deviation 11.98
Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose Baseline	74.54 beats per minute (bpm) Standard Deviation 10.50	75.26 beats per minute (bpm) Standard Deviation 11.03	75.08 beats per minute (bpm) Standard Deviation 11.10

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable ECG QTcF or PR Interval data.

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval QTcF interval, 26 weeks (n=241, 242, 236)	1.59 milliseconds (msec) Standard Error 1.13	0.29 milliseconds (msec) Standard Error 1.13	0.30 milliseconds (msec) Standard Error 1.12
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval PR interval, 26 weeks (n=238, 243, 236)	-1.13 milliseconds (msec) Standard Error 0.95	0.82 milliseconds (msec) Standard Error 0.95	-1.75 milliseconds (msec) Standard Error 0.94
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval PR interval, 52 weeks (n=220, 222, 221)	-0.43 milliseconds (msec) Standard Error 1.00	0.85 milliseconds (msec) Standard Error 1.00	0.05 milliseconds (msec) Standard Error 0.99
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval QTcF interval, 52 weeks (n= 222, 221, 221)	1.80 milliseconds (msec) Standard Error 1.14	1.89 milliseconds (msec) Standard Error 1.13	1.48 milliseconds (msec) Standard Error 1.13

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable ECG heart rate data.

Electrocardiogram (ECG) heart rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline value as a covariate.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=294 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate 52 weeks (n=230, 226, 230)	1.03 beats per minute (bpm) Standard Error 0.67	3.02 beats per minute (bpm) Standard Error 0.67	3.83 beats per minute (bpm) Standard Error 0.67
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate 26 weeks (n=244, 246, 243)	1.37 beats per minute (bpm) Standard Error 0.65	3.95 beats per minute (bpm) Standard Error 0.65	4.18 beats per minute (bpm) Standard Error 0.65

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.

The number of adjudicated (by an independent Clinical Endpoint Committee \[CEC\]) pancreatic events is summarized at 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose 4 weeks after last dose	NA events Data from 4 weeks after last dose was not analyzed for this outcome.	NA events Data from 4 weeks after last dose was not analyzed for this outcome.	NA events Data from 4 weeks after last dose was not analyzed for this outcome.
Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose 26 weeks	NA events Data from 26 weeks was not analyzed for this outcome.	NA events Data from 26 weeks was not analyzed for this outcome.	NA events Data from 26 weeks was not analyzed for this outcome.
Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose 52 weeks	0 events	0 events	0 events

SECONDARY outcome

Timeframe: Baseline through 26 weeks and 52 weeks

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

Hypoglycemic events (HE) were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions and had a plasma glucose \[PG\] of ≤ 70 milligrams per deciliter \[mg/dL\]), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a PG of ≤ 70 mg/dL), or asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL). The number of participants with self-reported hypoglycemic 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	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Documented Symptomatic HE, 26 weeks	243 participants	228 participants	242 participants
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Documented Symptomatic HE, 4 weeks after last dose	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Asymptomatic HE, 52 weeks	207 participants	191 participants	196 participants
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Asymptomatic HE, 4 weeks after last dose	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Total HE, 26 weeks	264 participants	250 participants	258 participants
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Total HE, 52 weeks	266 participants	252 participants	263 participants
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Total HE, 4 weeks after last dose	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Severe HE, 52 weeks	14 participants	8 participants	7 participants
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Severe HE, 4 weeks after last dose	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.	NA participants Data from 4 weeks after last dose was not analyzed for this outcome.
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Documented Symptomatic HE, 52 weeks	247 participants	235 participants	250 participants
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Asymptomatic HE, 26 weeks	198 participants	174 participants	179 participants
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose Severe HE, 26 weeks	9 participants	4 participants	5 participants

SECONDARY outcome

Timeframe: Baseline through 52 weeks

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

Hypoglycemic events (HE) were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions and had a plasma glucose \[PG\] of ≤ 70 milligrams per deciliter \[mg/dL\]), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a PG of ≤ 70 mg/dL), or asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Rate of Self-reported Hypoglycemic Events up to 52 Weeks Documented Symptomatic HE	39.90 events per participant per year Standard Deviation 50.92	30.98 events per participant per year Standard Deviation 39.64	35.03 events per participant per year Standard Deviation 44.94
Rate of Self-reported Hypoglycemic Events up to 52 Weeks Severe HE	0.08 events per participant per year Standard Deviation 0.43	0.03 events per participant per year Standard Deviation 0.19	0.05 events per participant per year Standard Deviation 0.50
Rate of Self-reported Hypoglycemic Events up to 52 Weeks Asymptomatic HE	14.20 events per participant per year Standard Deviation 23.19	9.55 events per participant per year Standard Deviation 19.52	11.56 events per participant per year Standard Deviation 24.69
Rate of Self-reported Hypoglycemic Events up to 52 Weeks Total HE	55.93 events per participant per year Standard Deviation 59.46	41.52 events per participant per year Standard Deviation 46.51	47.42 events per participant per year Standard Deviation 54.39

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.

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. 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	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks Any non-fatal cardiovascular event	11 participants	5 participants	6 participants
Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks Any cardiovascular event	12 participants	5 participants	6 participants
Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks Any fatal cardiovascular event	2 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline through 4 weeks after last dose

Population: Participants who received at least one dose of LY2189265 with evaluable LY2189265 ADA data.

A participant was considered to have treatment emergent LY2189265 anti-drug antibodies (ADA) if the participant had at least one titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.

Outcome measures

Outcome measures
Measure	Insulin Glargine Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=562 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose 26 weeks	—	NA participants Data from 26 weeks was not analyzed for this outcome.	—
Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose 52 weeks	—	NA participants Data from 52 weeks was not analyzed for this outcome.	—
Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose 4 weeks after last dose	—	9 participants	—

SECONDARY outcome

Timeframe: Baseline through 26 weeks, 52 weeks, and 4 weeks after last dose

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.

A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 26 weeks, 52 weeks, and 4 weeks after last dose. 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	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose 26 weeks	178 participants	203 participants	216 participants
Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose 4 weeks after last dose	211 participants	223 participants	235 participants
Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose 52 weeks	206 participants	217 participants	230 participants

Adverse Events

1.5 mg LY2189265

Serious events: 27 serious events

Other events: 219 other events

Deaths: 0 deaths

0.75 mg LY2189265

Serious events: 46 serious events

Other events: 232 other events

Deaths: 0 deaths

Insulin Glargine

Serious events: 53 serious events

Other events: 203 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1.5 mg LY2189265 n=295 participants at risk LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 participants at risk LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	Insulin Glargine n=296 participants at risk Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Blood and lymphatic system disorders Anaemia	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Blood and lymphatic system disorders Hemorrhagic anemia	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Blood and lymphatic system disorders Iron deficiency anemia	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Acute myocardial infarction	0.00% 0/295	0.00% 0/293	0.68% 2/296 • Number of events 3
Cardiac disorders Angina pectoris	0.34% 1/295 • Number of events 1	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Angina unstable	0.68% 2/295 • Number of events 2	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Arteriosclerosis coronary artery	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Cardiac disorders Atrial fibrillation	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Cardiac disorders Atrial flutter	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Cardiac disorders Atrioventricular block complete	0.00% 0/295	0.34% 1/293 • Number of events 1	0.34% 1/296 • Number of events 1
Cardiac disorders Atrioventricular block third degree	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Bradycardia	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Cardiac failure	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Cardiac failure congestive	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Cardiac disorders Cardiac pain	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Cardiogenic shock	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Chest pain - cardiac	0.34% 1/295 • Number of events 1	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Congestive heart failure	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Cardiac disorders Coronary artery disease	0.34% 1/295 • Number of events 1	0.00% 0/293	1.0% 3/296 • Number of events 3
Cardiac disorders Coronary artery insufficiency	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Cardiac disorders Coronary atherosclerosis	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Cardiac disorders Coronary insufficiency	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Cardiac disorders Decompensated heart failure	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Fibrillation ventricular	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Heart block third degree	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Cardiac disorders Infarct myocardial	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Cardiac disorders Myocardial infarction	0.34% 1/295 • Number of events 1	0.00% 0/293	0.68% 2/296 • Number of events 2
Cardiac disorders Non st segment elevation myocardial infarction	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Non stemi	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 2
Cardiac disorders Non-sustained ventricular tachycardia	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Cardiac disorders Unstable angina	0.68% 2/295 • Number of events 2	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Ventricular fibrillation	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Cardiac disorders Ventricular tachycardia	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Eye disorders Retinal detachment	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Eye disorders Retinal haemorrhage	0.00% 0/295	0.34% 1/293 • Number of events 1	0.34% 1/296 • Number of events 1
Eye disorders Retinal hemorrhage	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Gastrointestinal disorders Abdominal hernia	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Gastrointestinal disorders Abdominal herniation	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Gastrointestinal disorders Chronic diarrhea	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Gastrointestinal disorders Colitis	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Gastrointestinal disorders Colonic polyp	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Gastrointestinal disorders Diarrhoea	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Gastrointestinal disorders Gastroenteritis noninfectious	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Gastrointestinal disorders Gastrointestinal bleeding	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Gastrointestinal disorders Gastrointestinal inflammation	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Gastrointestinal disorders Hemorrhoidal bleeding	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Gastrointestinal disorders Ileus paralytic	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Gastrointestinal disorders Paralytic ileus	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
General disorders Chest pain	0.34% 1/295 • Number of events 1	0.00% 0/293	0.34% 1/296 • Number of events 1
General disorders Chest pain exertional	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
General disorders Death	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
General disorders Generalised oedema	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
General disorders Generalized edema	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
General disorders Multi-organ failure	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
General disorders Multiple organ failure	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
General disorders Non-cardiac chest pain	0.00% 0/295	0.34% 1/293 • Number of events 1	0.34% 1/296 • Number of events 1
Hepatobiliary disorders Acute cholecystitis	0.34% 1/295 • Number of events 1	0.00% 0/293	0.34% 1/296 • Number of events 1
Hepatobiliary disorders Cholecystitis acute	0.34% 1/295 • Number of events 1	0.00% 0/293	0.34% 1/296 • Number of events 1
Hepatobiliary disorders Cholelithiasis	0.00% 0/295	0.68% 2/293 • Number of events 2	0.00% 0/296
Infections and infestations Acute sinusitis	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Infections and infestations Ancylostomiasis	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Infections and infestations Appendicitis	0.00% 0/295	0.34% 1/293 • Number of events 1	0.34% 1/296 • Number of events 1
Infections and infestations Cellulitis	0.00% 0/295	0.68% 2/293 • Number of events 2	0.34% 1/296 • Number of events 1
Infections and infestations Cellulitis of foot	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Infections and infestations Cellulitis of leg	0.00% 0/295	0.34% 1/293 • Number of events 1	0.34% 1/296 • Number of events 1
Infections and infestations Cystitis	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Infections and infestations Epiglottitis	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Infections and infestations Erysipelas	0.34% 1/295 • Number of events 1	0.00% 0/293	0.34% 1/296 • Number of events 1
Infections and infestations Gangrenous appendicitis	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Infections and infestations Gastroenteritis	0.00% 0/295	0.68% 2/293 • Number of events 2	0.00% 0/296
Infections and infestations Gastroenteritis norovirus	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Infections and infestations Hookworm infection	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Infections and infestations Infected bites	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Infections and infestations Infected toe	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Infections and infestations Localised infection	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Infections and infestations Osteomyelitis	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Infections and infestations Pleurisy viral	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Infections and infestations Pneumonia	0.34% 1/295 • Number of events 1	1.4% 4/293 • Number of events 5	0.34% 1/296 • Number of events 1
Infections and infestations Sepsis	0.34% 1/295 • Number of events 1	0.34% 1/293 • Number of events 1	0.00% 0/296
Infections and infestations Staphylococcal sepsis	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Infections and infestations Staphylococcus aureus septicemia	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Infections and infestations Supraglottitis	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Infections and infestations Urinary infection	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Infections and infestations Urinary tract infection	0.00% 0/295	0.68% 2/293 • Number of events 2	0.00% 0/296
Injury, poisoning and procedural complications Back injury	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Injury, poisoning and procedural complications Fall	0.00% 0/295	0.34% 1/293 • Number of events 1	0.34% 1/296 • Number of events 1
Injury, poisoning and procedural complications Falling	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Injury, poisoning and procedural complications Fractured ribs	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Injury, poisoning and procedural complications Fractured sternum	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Injury, poisoning and procedural complications Knee fracture	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Injury, poisoning and procedural complications Leg injury	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Injury, poisoning and procedural complications Limb injury	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Injury, poisoning and procedural complications Lumbar vertebral fracture l1	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Injury, poisoning and procedural complications Meniscus lesion	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Injury, poisoning and procedural complications Meniscus tear	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Injury, poisoning and procedural complications Muscle rupture	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Injury, poisoning and procedural complications Quadriceps tendon rupture	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Injury, poisoning and procedural complications Rib fracture	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Injury, poisoning and procedural complications Sternal fracture	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Injury, poisoning and procedural complications Suture related complication	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Injury, poisoning and procedural complications Tendon rupture	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Injury, poisoning and procedural complications Torn muscle	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Metabolism and nutrition disorders Dehydration	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Metabolism and nutrition disorders Hyperglycaemia	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Metabolism and nutrition disorders Hyperglycemia	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Metabolism and nutrition disorders Hypoglycaemia	1.0% 3/295 • Number of events 3	2.7% 8/293 • Number of events 17	0.34% 1/296 • Number of events 1
Metabolism and nutrition disorders Hypoglycemia	2.0% 6/295 • Number of events 7	2.4% 7/293 • Number of events 16	4.1% 12/296 • Number of events 20
Metabolism and nutrition disorders Hypoglycemic episode	0.34% 1/295 • Number of events 1	0.34% 1/293 • Number of events 1	0.68% 2/296 • Number of events 3
Musculoskeletal and connective tissue disorders Back pain	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Musculoskeletal and connective tissue disorders Cervical pain	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Musculoskeletal and connective tissue disorders Lumbar pain	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Musculoskeletal and connective tissue disorders Muscle atrophy	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Musculoskeletal and connective tissue disorders Muscle weakness	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Musculoskeletal and connective tissue disorders Muscular weakness	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Musculoskeletal and connective tissue disorders Neck pain	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Musculoskeletal and connective tissue disorders Osteoarthritis aggravated	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/295	0.34% 1/293 • Number of events 2	0.00% 0/296
Musculoskeletal and connective tissue disorders Rotator cuff tear	0.00% 0/295	0.34% 1/293 • Number of events 2	0.00% 0/296
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder adenocarcinoma	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/160	0.68% 1/148 • Number of events 1	0.00% 0/165
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal neoplasm	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Amyotrophic lateral sclerosis	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Nervous system disorders Carotid artery disease	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Nervous system disorders Carpal tunnel syndrome	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 2
Nervous system disorders Cerebellar infarction	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Cerebrovascular accident	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Nervous system disorders Haemorrhagic stroke	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Hemorrhagic stroke	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Hydrocephalus	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Hypoglycaemic coma	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Nervous system disorders Hypoglycemic coma	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Nervous system disorders Ischaemic stroke	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Nervous system disorders Ischemic stroke	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Nervous system disorders Lumboischialgia	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Metabolic encephalopathy	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Nervous system disorders Orthostatic collapse	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Palsy bells	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Sciatica	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Stroke	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Nervous system disorders Syncope	0.00% 0/295	0.68% 2/293 • Number of events 2	0.00% 0/296
Nervous system disorders Transient cerebral ischemia	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Transient ischaemic attack	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Nervous system disorders Unilateral carpal tunnel syndrome	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 2
Nervous system disorders Viith nerve paralysis	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Psychiatric disorders Confusional state	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Psychiatric disorders Depression	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Psychiatric disorders Major depression	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Psychiatric disorders Mental confusion	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Psychiatric disorders Psychosis	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Psychiatric disorders Psychotic disorder	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Renal and urinary disorders Calculus ureteric	0.34% 1/295 • Number of events 1	0.68% 2/293 • Number of events 2	0.00% 0/296
Renal and urinary disorders Hydronephrosis	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Renal and urinary disorders Nephrolithiasis	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Renal and urinary disorders Pyuria	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Renal and urinary disorders Renal artery stenosis	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Renal and urinary disorders Renal stone	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Renal and urinary disorders Unilateral renal artery stenosis	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Renal and urinary disorders Ureteral calculus	0.00% 0/295	0.68% 2/293 • Number of events 2	0.00% 0/296
Renal and urinary disorders Ureteric calculus	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/160	0.68% 1/148 • Number of events 1	0.00% 0/165
Reproductive system and breast disorders Menorrhagia	0.00% 0/135	0.00% 0/145	0.76% 1/131 • Number of events 1
Reproductive system and breast disorders Premenopausal menorrhagia	0.00% 0/135	0.00% 0/145	0.76% 1/131 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/295	0.68% 2/293 • Number of events 2	0.00% 0/296
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.00% 0/295	0.34% 1/293 • Number of events 1	0.00% 0/296
Vascular disorders Arteriosclerosis	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Vascular disorders Atherosclerosis generalized	0.34% 1/295 • Number of events 1	0.00% 0/293	0.00% 0/296
Vascular disorders Bleeding	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Vascular disorders Haemorrhage	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Vascular disorders Hypertension	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1
Vascular disorders Hypertensive emergency	0.00% 0/295	0.00% 0/293	0.34% 1/296 • Number of events 1

Other adverse events

Other adverse events
Measure	1.5 mg LY2189265 n=295 participants at risk LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 participants at risk LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	Insulin Glargine n=296 participants at risk Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Gastrointestinal disorders Abdominal pain upper	4.4% 13/295 • Number of events 17	0.68% 2/293 • Number of events 3	0.68% 2/296 • Number of events 2
Gastrointestinal disorders Constipation	4.1% 12/295 • Number of events 12	2.0% 6/293 • Number of events 6	1.7% 5/296 • Number of events 5
Gastrointestinal disorders Diarrhea	14.9% 44/295 • Number of events 62	11.6% 34/293 • Number of events 67	5.1% 15/296 • Number of events 18
Gastrointestinal disorders Dyspepsia	3.7% 11/295 • Number of events 11	1.0% 3/293 • Number of events 3	0.34% 1/296 • Number of events 1
Gastrointestinal disorders Gastrooesophageal reflux disease	0.34% 1/295 • Number of events 1	3.8% 11/293 • Number of events 12	1.7% 5/296 • Number of events 5
Gastrointestinal disorders Heartburn	4.4% 13/295 • Number of events 13	1.4% 4/293 • Number of events 4	0.34% 1/296 • Number of events 1
Gastrointestinal disorders Nausea	25.8% 76/295 • Number of events 115	17.7% 52/293 • Number of events 74	3.0% 9/296 • Number of events 11
Gastrointestinal disorders Vomiting	11.9% 35/295 • Number of events 46	10.6% 31/293 • Number of events 49	1.7% 5/296 • Number of events 5
General disorders Fatigue	3.7% 11/295 • Number of events 11	2.4% 7/293 • Number of events 7	1.7% 5/296 • Number of events 6
General disorders Oedema peripheral	2.4% 7/295 • Number of events 7	5.8% 17/293 • Number of events 20	3.0% 9/296 • Number of events 9
Infections and infestations Bronchitis	2.4% 7/295 • Number of events 8	3.1% 9/293 • Number of events 11	4.4% 13/296 • Number of events 15
Infections and infestations Common cold	6.4% 19/295 • Number of events 23	9.6% 28/293 • Number of events 37	8.8% 26/296 • Number of events 33
Infections and infestations Flu syndrome	1.4% 4/295 • Number of events 6	3.1% 9/293 • Number of events 11	0.68% 2/296 • Number of events 2
Infections and infestations Nasopharyngitis	7.5% 22/295 • Number of events 27	0.34% 1/293 • Number of events 1	11.1% 33/296 • Number of events 43
Infections and infestations Upper respiratory tract infection	1.0% 3/295 • Number of events 5	0.68% 2/293 • Number of events 3	3.7% 11/296 • Number of events 12
Infections and infestations Urinary tract infection	4.1% 12/295 • Number of events 14	4.8% 14/293 • Number of events 16	3.7% 11/296 • Number of events 18
Metabolism and nutrition disorders Anorexia	3.7% 11/295 • Number of events 12	1.7% 5/293 • Number of events 5	0.00% 0/296
Metabolism and nutrition disorders Decreased appetite	3.4% 10/295 • Number of events 10	2.7% 8/293 • Number of events 10	0.00% 0/296
Metabolism and nutrition disorders Dyslipidaemia	3.4% 10/295 • Number of events 10	1.7% 5/293 • Number of events 5	1.7% 5/296 • Number of events 5
Metabolism and nutrition disorders Dyslipidemia	3.4% 10/295 • Number of events 10	1.7% 5/293 • Number of events 5	1.7% 5/296 • Number of events 5
Musculoskeletal and connective tissue disorders Arthralgia	0.34% 1/295 • Number of events 1	1.4% 4/293 • Number of events 4	5.4% 16/296 • Number of events 21
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.1% 9/295 • Number of events 9	0.34% 1/293 • Number of events 1	3.0% 9/296 • Number of events 9
Musculoskeletal and connective tissue disorders Pain in extremity	3.1% 9/295 • Number of events 9	4.4% 13/293 • Number of events 14	2.7% 8/296 • Number of events 10
Musculoskeletal and connective tissue disorders Shoulder pain	3.1% 9/295 • Number of events 9	1.4% 4/293 • Number of events 4	3.0% 9/296 • Number of events 9
Nervous system disorders Headache	5.4% 16/295 • Number of events 19	6.8% 20/293 • Number of events 27	5.7% 17/296 • Number of events 20
Vascular disorders Hypertension	1.7% 5/295 • Number of events 5	2.7% 8/293 • Number of events 8	3.0% 9/296 • Number of events 9

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

Measure	Insulin Glargine n=296 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	1.5 mg LY2189265 n=295 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	0.75 mg LY2189265 n=293 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Bedtime, 52 weeks (n=195, 205, 213)	-3.27 millimoles per liter (mmol/L)] Standard Error 0.17	-3.62 millimoles per liter (mmol/L)] Standard Error 0.17	-3.96 millimoles per liter (mmol/L)] Standard Error 0.17
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Pre-morning meal, 26 weeks (n=228, 231, 232)	-2.01 millimoles per liter (mmol/L)] Standard Error 0.14	-0.36 millimoles per liter (mmol/L)] Standard Error 0.14	-0.06 millimoles per liter (mmol/L)] Standard Error 0.14
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Post-morning meal, 26 weeks (n=220, 227, 229)	-4.03 millimoles per liter (mmol/L)] Standard Error 0.18	-3.70 millimoles per liter (mmol/L)] Standard Error 0.19	-3.29 millimoles per liter (mmol/L)] Standard Error 0.19
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Pre-midday meal, 26 weeks (n=227, 231, 233)	-2.65 millimoles per liter (mmol/L)] Standard Error 0.16	-2.80 millimoles per liter (mmol/L)] Standard Error 0.16	-2.38 millimoles per liter (mmol/L)] Standard Error 0.16
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Post-midday meal, 26 weeks (n=219, 227, 228)	-3.70 millimoles per liter (mmol/L)] Standard Error 0.17	-4.51 millimoles per liter (mmol/L)] Standard Error 0.17	-4.53 millimoles per liter (mmol/L)] Standard Error 0.17
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Pre-evening meal, 26 weeks (n=226, 231, 232)	-2.74 millimoles per liter (mmol/L)] Standard Error 0.16	-3.24 millimoles per liter (mmol/L)] Standard Error 0.16	-3.06 millimoles per liter (mmol/L)] Standard Error 0.16
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Post-evening meal, 26 weeks (n=220, 228, 227)	-3.90 millimoles per liter (mmol/L)] Standard Error 0.17	-4.61 millimoles per liter (mmol/L)] Standard Error 0.17	-4.54 millimoles per liter (mmol/L)] Standard Error 0.17
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Bedtime, 26 weeks (n=220, 221, 226)	-3.40 millimoles per liter (mmol/L)] Standard Error 0.17	-4.00 millimoles per liter (mmol/L)] Standard Error 0.17	-3.89 millimoles per liter (mmol/L)] Standard Error 0.17
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles After bedtime, 26 weeks (n=208, 216, 208)	-1.96 millimoles per liter (mmol/L)] Standard Error 0.15	-1.48 millimoles per liter (mmol/L)] Standard Error 0.15	-1.50 millimoles per liter (mmol/L)] Standard Error 0.15
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Daily Mean, 26 weeks (n=202, 206, 199)	-3.10 millimoles per liter (mmol/L)] Standard Error 0.12	-3.17 millimoles per liter (mmol/L)] Standard Error 0.12	-2.97 millimoles per liter (mmol/L)] Standard Error 0.12
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Pre-morning meal, 52 weeks (n=207, 213, 218)	-2.02 millimoles per liter (mmol/L)] Standard Error 0.15	0.03 millimoles per liter (mmol/L)] Standard Error 0.16	0.05 millimoles per liter (mmol/L)] Standard Error 0.15
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Post-morning meal, 52 weeks (n=200, 211, 211)	-3.76 millimoles per liter (mmol/L)] Standard Error 0.19	-3.38 millimoles per liter (mmol/L)] Standard Error 0.19	-3.23 millimoles per liter (mmol/L)] Standard Error 0.19
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Pre-midday meal, 52 weeks (n=207, 213, 218)	-2.63 millimoles per liter (mmol/L)] Standard Error 0.14	-2.53 millimoles per liter (mmol/L)] Standard Error 0.14	-2.52 millimoles per liter (mmol/L)] Standard Error 0.14
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Post-midday meal, 52 weeks (n=202, 210, 212)	-3.83 millimoles per liter (mmol/L)] Standard Error 0.18	-4.33 millimoles per liter (mmol/L)] Standard Error 0.18	-4.29 millimoles per liter (mmol/L)] Standard Error 0.18
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Pre-evening meal, 52 weeks (n=207, 214, 217)	-2.67 millimoles per liter (mmol/L)] Standard Error 0.16	3.00 millimoles per liter (mmol/L)] Standard Error 0.16	-3.07 millimoles per liter (mmol/L)] Standard Error 0.16
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Post-evening meal, 52 weeks (n=200, 210, 212)	-3.71 millimoles per liter (mmol/L)] Standard Error 0.16	-4.22 millimoles per liter (mmol/L)] Standard Error 0.17	-4.54 millimoles per liter (mmol/L)] Standard Error 0.17
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles After bedtime, 52 weeks (n=192, 192 197)	-1.80 millimoles per liter (mmol/L)] Standard Error 0.15	-1.17 millimoles per liter (mmol/L)] Standard Error 0.15	-1.36 millimoles per liter (mmol/L)] Standard Error 0.15
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles Daily Mean, 52 weeks (n=182, 185, 189)	-2.97 millimoles per liter (mmol/L)] Standard Error 0.12	-2.84 millimoles per liter (mmol/L)] Standard Error 0.12	-2.95 millimoles per liter (mmol/L)] Standard Error 0.12