Trial Outcomes & Findings for A Study in Participants With Type 2 Diabetes Mellitus (AWARD-2) (NCT NCT01075282)

Last Updated: 2015-01-16

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

810 participants

Primary outcome timeframe

Baseline, 52 weeks

Results posted on

2015-01-16

Participant Flow

Participant milestones

Participant milestones
Measure	LY2189265 1.5 mg LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Overall Study STARTED	273	272	265
Overall Study Received at Least One Dose of Study Drug	273	272	262
Overall Study COMPLETED	242	243	238
Overall Study NOT COMPLETED	31	29	27

Reasons for withdrawal

Reasons for withdrawal
Measure	LY2189265 1.5 mg LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Overall Study Withdrawal by Subject	11	7	11
Overall Study Adverse Event	9	8	5
Overall Study Entry Criteria Not Met	3	2	0
Overall Study Lost to Follow-up	3	3	3
Overall Study Physician Decision	3	3	3
Overall Study Lack of Efficacy	1	1	0
Overall Study Treatment Non-compliance	1	2	2
Overall Study Protocol Violation	0	2	1
Overall Study Death	0	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Total n=807 Participants Total of all reporting groups
Age, Continuous	56.24 years STANDARD_DEVIATION 9.76 • n=5 Participants	56.56 years STANDARD_DEVIATION 9.27 • n=7 Participants	57.21 years STANDARD_DEVIATION 9.38 • n=5 Participants	56.66 years STANDARD_DEVIATION 9.47 • n=4 Participants
Sex: Female, Male Female	129 Participants n=5 Participants	136 Participants n=7 Participants	128 Participants n=5 Participants	393 Participants n=4 Participants
Sex: Female, Male Male	144 Participants n=5 Participants	136 Participants n=7 Participants	134 Participants n=5 Participants	414 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	98 Participants n=5 Participants	96 Participants n=7 Participants	97 Participants n=5 Participants	291 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	175 Participants n=5 Participants	176 Participants n=7 Participants	165 Participants n=5 Participants	516 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	29 Participants n=5 Participants	31 Participants n=7 Participants	29 Participants n=5 Participants	89 Participants n=4 Participants
Race (NIH/OMB) Asian	48 Participants n=5 Participants	46 Participants n=7 Participants	43 Participants n=5 Participants	137 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	193 Participants n=5 Participants	193 Participants n=7 Participants	184 Participants n=5 Participants	570 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Taiwan	13 participants n=5 Participants	13 participants n=7 Participants	12 participants n=5 Participants	38 participants n=4 Participants
Region of Enrollment Slovakia	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment Greece	6 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants	19 participants n=4 Participants
Region of Enrollment Spain	10 participants n=5 Participants	12 participants n=7 Participants	13 participants n=5 Participants	35 participants n=4 Participants
Region of Enrollment Italy	2 participants n=5 Participants	3 participants n=7 Participants	1 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment India	30 participants n=5 Participants	27 participants n=7 Participants	27 participants n=5 Participants	84 participants n=4 Participants
Region of Enrollment France	2 participants n=5 Participants	3 participants n=7 Participants	1 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment Czech Republic	12 participants n=5 Participants	14 participants n=7 Participants	13 participants n=5 Participants	39 participants n=4 Participants
Region of Enrollment Hungary	16 participants n=5 Participants	16 participants n=7 Participants	15 participants n=5 Participants	47 participants n=4 Participants
Region of Enrollment Mexico	29 participants n=5 Participants	28 participants n=7 Participants	27 participants n=5 Participants	84 participants n=4 Participants
Region of Enrollment Canada	26 participants n=5 Participants	25 participants n=7 Participants	24 participants n=5 Participants	75 participants n=4 Participants
Region of Enrollment Argentina	55 participants n=5 Participants	54 participants n=7 Participants	54 participants n=5 Participants	163 participants n=4 Participants
Region of Enrollment Belgium	7 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	15 participants n=4 Participants
Region of Enrollment Brazil	6 participants n=5 Participants	5 participants n=7 Participants	7 participants n=5 Participants	18 participants n=4 Participants
Region of Enrollment Poland	16 participants n=5 Participants	18 participants n=7 Participants	17 participants n=5 Participants	51 participants n=4 Participants
Region of Enrollment Croatia	3 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment Romania	23 participants n=5 Participants	22 participants n=7 Participants	22 participants n=5 Participants	67 participants n=4 Participants
Region of Enrollment Australia	13 participants n=5 Participants	13 participants n=7 Participants	13 participants n=5 Participants	39 participants n=4 Participants
Region of Enrollment Sweden	2 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment Korea, Republic of	1 participants n=5 Participants	3 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants
Body Weight	85.13 kilograms STANDARD_DEVIATION 17.90 • n=5 Participants	86.18 kilograms STANDARD_DEVIATION 18.15 • n=7 Participants	87.66 kilograms STANDARD_DEVIATION 19.62 • n=5 Participants	86.31 kilograms STANDARD_DEVIATION 18.56 • n=4 Participants
Body Mass Index (BMI)	31.23 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.21 • n=5 Participants	31.51 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.41 • n=7 Participants	31.91 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.76 • n=5 Participants	31.55 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.46 • n=4 Participants
Glycosylated Hemoglobin (HbA1c)	8.18 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.03 • n=5 Participants	8.13 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.98 • n=7 Participants	8.10 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.95 • n=5 Participants	8.14 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.99 • n=4 Participants
Duration of Diabetes	9.13 years STANDARD_DEVIATION 6.22 • n=5 Participants	9.28 years STANDARD_DEVIATION 5.93 • n=7 Participants	8.87 years STANDARD_DEVIATION 5.98 • n=5 Participants	9.10 years STANDARD_DEVIATION 6.04 • n=4 Participants
Fasting Serum Glucose	9.16 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.73 • n=5 Participants	8.96 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.70 • n=7 Participants	9.08 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.66 • n=5 Participants	9.07 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.69 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, 52 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 were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=263 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=267 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=259 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)	-1.08 percentage of glycosylated hemoglobin Standard Error 0.06	-0.76 percentage of glycosylated hemoglobin Standard Error 0.06	-0.63 percentage of glycosylated hemoglobin Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline, 26 weeks, and 78 weeks

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

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) 26 weeks (n=263, 266, 258)	-1.16 percent Standard Error 0.06	-0.89 percent Standard Error 0.05	-0.65 percent Standard Error 0.06
Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) 78 weeks (n=263, 267, 259)	-0.90 percent Standard Error 0.07	-0.62 percent Standard Error 0.07	-0.59 percent Standard Error 0.07

SECONDARY outcome

Timeframe: 26, 52, and 78 weeks

Number of participants achieving HbA1c levels less than 7.0% was analyzed with a logistic regression model with baseline, country, and treatment as factors included in the model.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks 26 weeks (n=263, 266, 258)	153 participants	122 participants	84 participants
Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks 52 weeks (n=263, 267, 259)	140 participants	99 participants	80 participants
Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks 78 weeks (n=263, 267, 259)	129 participants	91 participants	79 participants

SECONDARY outcome

Timeframe: 26, 52, and 78 weeks

Number of participants achieving HbA1c levels less than or equal to 6.5% was analyzed with a logistic regression model with baseline, country, and treatment as factors included in the model.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks 52 weeks (n=263, 267, 259)	71 participants	60 participants	35 participants
Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks 26 weeks (n=263, 266, 258)	97 participants	74 participants	40 participants
Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks 78 weeks (n=263, 267, 259)	74 participants	59 participants	43 participants

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 weeks

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

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

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=231 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=242 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=228 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles 26 weeks (n=199, 204, 190)	-1.79 millimoles per liter (mmol/L) Standard Error 0.10	-1.46 millimoles per liter (mmol/L) Standard Error 0.10	-1.58 millimoles per liter (mmol/L) Standard Error 0.10
Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles 52 weeks (n=180, 185, 176)	-1.69 millimoles per liter (mmol/L) Standard Error 0.11	-1.32 millimoles per liter (mmol/L) Standard Error 0.11	-1.44 millimoles per liter (mmol/L) Standard Error 0.11
Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles 78 weeks (n=172, 164, 168)	-1.55 millimoles per liter (mmol/L) Standard Error 0.13	-1.15 millimoles per liter (mmol/L) Standard Error 0.12	-1.47 millimoles per liter (mmol/L) Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, 52, and 78 weeks

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

The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S), as percentages of a normal reference population (normal young adults). The normal reference population for both HOMA2-B and HOMA-2S were set at 100%. Least Squares (LS) means of change from baseline of C-peptide based HOMA2-%B and HOMA2-%S were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=222 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=230 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) HOMA2-%S, 52 weeks (n=175,181)	-2.89 percentage of HOMA2 Standard Error 1.21	-2.66 percentage of HOMA2 Standard Error 1.19	—
Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) HOMA2-%B, 52 weeks (n=175, 181)	29.95 percentage of HOMA2 Standard Error 4.61	24.60 percentage of HOMA2 Standard Error 4.51	—
Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) HOMA2-%B, 78 weeks (n=167, 165)	28.54 percentage of HOMA2 Standard Error 4.78	15.66 percentage of HOMA2 Standard Error 4.75	—
Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) HOMA2-%S, 78 weeks (n=167, 165)	-2.64 percentage of HOMA2 Standard Error 1.23	-3.62 percentage of HOMA2 Standard Error 1.23	—

SECONDARY outcome

Timeframe: Baseline, 52, and 78 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable glucagon 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) with country and treatment as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=235 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=235 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=232 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 52 and 78 Weeks in Glucagon Concentration 52 weeks (n=232, 231, 228)	-3.91 picomoles per liter (pmol/L) Standard Error 0.47	-3.31 picomoles per liter (pmol/L) Standard Error 0.47	-3.85 picomoles per liter (pmol/L) Standard Error 0.47
Change From Baseline to 52 and 78 Weeks in Glucagon Concentration 78 weeks (n=235, 235, 232)	-3.57 picomoles per liter (pmol/L) Standard Error 0.47	-3.37 picomoles per liter (pmol/L) Standard Error 0.47	-3.65 picomoles per liter (pmol/L) Standard Error 0.47

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 weeks

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

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

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=272 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=270 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=259 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks for Body Weight 26 weeks	-1.82 kilogram (kg) Standard Error 0.20	-1.47 kilogram (kg) Standard Error 0.20	1.01 kilogram (kg) Standard Error 0.20
Change From Baseline to 26, 52 and 78 Weeks for Body Weight 52 weeks	-1.87 kilogram (kg) Standard Error 0.24	-1.33 kilogram (kg) Standard Error 0.24	1.44 kilogram (kg) Standard Error 0.24
Change From Baseline to 26, 52 and 78 Weeks for Body Weight 78 weeks	-1.96 kilogram (kg) Standard Error 0.26	-1.54 kilogram (kg) Standard Error 0.26	1.28 kilogram (kg) Standard Error 0.26

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 weeks

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

Body mass index (BMI) 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index 26 weeks (n=257, 261, 245)	-0.64 kilograms per square meter (kg/m^2) Standard Error 0.07	-0.50 kilograms per square meter (kg/m^2) Standard Error 0.07	0.44 kilograms per square meter (kg/m^2) Standard Error 0.07
Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index 52 weeks (n=250, 252, 238)	-0.64 kilograms per square meter (kg/m^2) Standard Error 0.08	-0.39 kilograms per square meter (kg/m^2) Standard Error 0.08	0.62 kilograms per square meter (kg/m^2) Standard Error 0.08
Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index 78 weeks (n=246, 244, 238)	-0.64 kilograms per square meter (kg/m^2) Standard Error 0.09	-0.39 kilograms per square meter (kg/m^2) Standard Error 0.09	0.59 kilograms per square meter (kg/m^2) Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 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 European Quality of Life - 5 dimensions (EQ-5D) questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part of the questionnaire consists of a 100-mm visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) and adjusted by treatment, country, and baseline.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension VAS, 26 weeks (n=253, 252, 243)	3.3 units on a scale Standard Error 0.83	3.4 units on a scale Standard Error 0.84	0.8 units on a scale Standard Error 0.86
Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension EQ-5D UK, 26 weeks (n=257, 254, 249)	0.01 units on a scale Standard Error 0.01	0.00 units on a scale Standard Error 0.01	-0.01 units on a scale Standard Error 0.01
Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension EQ-5D UK, 52 weeks (n=259, 260, 253)	0.01 units on a scale Standard Error 0.01	0.00 units on a scale Standard Error 0.01	-0.04 units on a scale Standard Error 0.01
Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension EQ-5D UK, 78 weeks (n=259, 260, 253)	0.01 units on a scale Standard Error 0.01	0.00 units on a scale Standard Error 0.01	0.00 units on a scale Standard Error 0.01
Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension VAS, 52 weeks (n=260, 258, 252)	3.2 units on a scale Standard Error 0.85	2.3 units on a scale Standard Error 0.85	1.1 units on a scale Standard Error 0.88
Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension VAS, 78 weeks (n=260, 258, 252)	3.8 units on a scale Standard Error 0.85	3.2 units on a scale Standard Error 0.85	2.2 units on a scale Standard Error 0.89

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 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 and treatment as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=260 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living 26 weeks (n=256, 256, 248)	0.7 units on a scale Standard Error 0.30	0.1 units on a scale Standard Error 0.30	-0.3 units on a scale Standard Error 0.30
Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living 52 weeks (n=260, 261, 249)	0.9 units on a scale Standard Error 0.31	0.4 units on a scale Standard Error 0.31	-0.6 units on a scale Standard Error 0.32
Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living 78 weeks (n=260, 261, 249)	1.0 units on a scale Standard Error 0.31	0.3 units on a scale Standard Error 0.31	-0.3 units on a scale Standard Error 0.32

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 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 and treatment as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception 78 weeks (n=260, 261, 252)	0.5 units on a scale Standard Error 0.16	0.3 units on a scale Standard Error 0.15	0.1 units on a scale Standard Error 0.16
Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception 26 weeks (n=258, 258, 251)	0.1 units on a scale Standard Error 0.16	0.2 units on a scale Standard Error 0.16	-0.1 units on a scale Standard Error 0.16
Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception 52 weeks (n=260, 261, 252)	0.5 units on a scale Standard Error 0.16	0.2 units on a scale Standard Error 0.16	0.1 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 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 and treatment as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=270 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=271 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=255 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey 26 weeks (n=255, 255, 244)	-2.8 units on a scale Standard Error 0.95	-2.4 units on a scale Standard Error 0.96	0.3 units on a scale Standard Error 0.98
Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey 52 weeks (n=258, 259, 245)	-4.2 units on a scale Standard Error 0.83	-4.1 units on a scale Standard Error 0.83	-1.0 units on a scale Standard Error 0.86
Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey 78 weeks (n=258, 259, 245)	-4.6 units on a scale Standard Error 0.82	-4.7 units on a scale Standard Error 0.82	-2.0 units on a scale Standard Error 0.85

SECONDARY outcome

Timeframe: 26, 52, and 78 weeks

Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine. The number of participants with at least 1 TEAE is reported.

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, 52, and 78 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	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks 26 weeks	160 participants	146 participants	137 participants
Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks 52 weeks	189 participants	175 participants	175 participants
Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks 78 weeks	201 participants	188 participants	192 participants

SECONDARY outcome

Timeframe: Baseline through 26, 52, and 78 weeks

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

Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =\<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =\<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events is summarized cumulatively at 26, 52, and 78 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	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Documented symptomatic HE, 52 weeks	515 events	444 events	789 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Asymptomatic HE, 52 weeks	757 events	709 events	1093 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Nocturnal HE, 52 weeks	185 events	147 events	519 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Severe HE, 26 weeks	1 events	0 events	1 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Severe HE, 52 weeks	1 events	0 events	2 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Severe HE, 78 weeks	2 events	0 events	2 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Documented symptomatic HE, 26 weeks	311 events	315 events	447 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Documented symptomatic HE, 78 weeks	607 events	515 events	1033 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Asymptomatic HE, 26 weeks	500 events	484 events	609 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Asymptomatic HE, 78 weeks	884 events	911 events	1358 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Nocturnal HE, 26 weeks	145 events	117 events	240 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Nocturnal HE, 78 weeks	215 events	184 events	635 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Probable symptomatic HE, 26 weeks	11 events	19 events	20 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Probable symptomatic HE, 52 weeks	17 events	24 events	22 events
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Probable symptomatic HE, 78 weeks	20 events	28 events	26 events

SECONDARY outcome

Timeframe: Baseline through 26, 52, and 78 weeks

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

Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =\<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =\<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

SECONDARY outcome

Timeframe: 26, 52, and 78 weeks

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

Additional intervention was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. The number of participants requiring additional intervention due to hyperglycemia is summarized cumulatively at 26, 52, and 78 weeks.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks 26 weeks	2 participants	4 participants	0 participants
Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks 78 weeks	24 participants	34 participants	16 participants
Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks 52 weeks	11 participants	20 participants	8 participants

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 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) and lipase concentrations were measured.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=271 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=269 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=259 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes Amylase (total), 26 weeks	4.000 units/liter Interval -4.0 to 13.0	4.000 units/liter Interval -3.0 to 11.0	2.000 units/liter Interval -5.0 to 8.0
Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes Lipase, 52 weeks	4.000 units/liter Interval -3.0 to 12.0	4.000 units/liter Interval -2.0 to 11.0	-1.000 units/liter Interval -8.0 to 6.0
Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes Amylase (total), 52 weeks	4.000 units/liter Interval -4.0 to 11.0	5.000 units/liter Interval -3.0 to 13.0	3.000 units/liter Interval -5.0 to 9.0
Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes Amylase (total), 78 weeks	4.000 units/liter Interval -4.0 to 13.0	4.000 units/liter Interval -3.0 to 12.0	1.000 units/liter Interval -7.0 to 9.0
Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes Amylase (pancreas-derived), 26 weeks	3.000 units/liter Interval -1.0 to 8.0	3.000 units/liter Interval 0.0 to 7.0	1.000 units/liter Interval -2.0 to 4.0
Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes Amylase (pancreas-derived), 52 weeks	3.000 units/liter Interval -1.0 to 8.0	3.000 units/liter Interval -1.0 to 7.0	1.000 units/liter Interval -2.0 to 6.0
Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes Amylase (pancreas-derived), 78 weeks	2.000 units/liter Interval -2.0 to 7.0	2.000 units/liter Interval -1.0 to 7.0	0.000 units/liter Interval -3.0 to 4.0
Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes Lipase, 26 weeks	5.000 units/liter Interval -4.0 to 15.0	5.000 units/liter Interval -1.0 to 15.0	-1.000 units/liter Interval -6.0 to 5.0
Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes Lipase, 78 weeks	4.000 units/liter Interval -3.0 to 14.0	4.000 units/liter Interval -1.0 to 13.0	-2.000 units/liter Interval -8.0 to 5.0

SECONDARY outcome

Timeframe: Baseline through 26, 52, and 78 weeks

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

The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26, 52, and 78 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	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks 26 weeks	1 participants	1 participants	0 participants
Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks 52 weeks	2 participants	1 participants	0 participants
Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks 78 weeks	2 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 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	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin 78 weeks (n=267, 269, 259)	0.086 picogram/milliliter Standard Deviation 1.31	0.035 picogram/milliliter Standard Deviation 1.20	0.151 picogram/milliliter Standard Deviation 1.73
Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin 26 weeks (n=266, 267, 258)	0.163 picogram/milliliter Standard Deviation 1.31	0.097 picogram/milliliter Standard Deviation 1.20	0.149 picogram/milliliter Standard Deviation 1.30
Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin 52 weeks (n=266, 269, 259)	0.128 picogram/milliliter Standard Deviation 1.20	0.132 picogram/milliliter Standard Deviation 1.32	0.176 picogram/milliliter Standard Deviation 1.62

SECONDARY outcome

Timeframe: Baseline through 26, 52, and 78 weeks

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

Information on cardiovascular (CV) risk factors was collected at baseline. Data on any new CV event was prospectively collected using a CV event electronic case report form. At prespecified visits, participants were asked about any new CV event. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs to be adjudicated include myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with adjudicated CV events is summarized cumulatively at 26, 52, and 78 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	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks Any CV event, 52 weeks	3 participants	4 participants	6 participants
Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks Any non-fatal CV event, 52 weeks	3 participants	4 participants	5 participants
Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks Any CV event, 26 weeks	2 participants	1 participants	3 participants
Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks Any fatal CV event, 26 weeks	0 participants	0 participants	0 participants
Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks Any non-fatal CV event, 26 weeks	2 participants	1 participants	3 participants
Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks Any fatal CV event, 52 weeks	0 participants	0 participants	1 participants
Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks Any CV event, 78 week	3 participants	6 participants	9 participants
Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks Any fatal CV event, 78 week	0 participants	1 participants	1 participants
Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks Any non-fatal CV event, 78 week	3 participants	6 participants	8 participants

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 weeks

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

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

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate 26 weeks (n=257, 260, 245)	1.56 beats per minute (bpm) Standard Error 0.49	0.74 beats per minute (bpm) Standard Error 0.48	-1.21 beats per minute (bpm) Standard Error 0.50
Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate 52 weeks (n=250, 252, 240)	1.29 beats per minute (bpm) Standard Error 0.50	0.51 beats per minute (bpm) Standard Error 0.49	-0.52 beats per minute (bpm) Standard Error 0.51
Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate 78 weeks (n=246, 244, 238)	1.31 beats per minute (bpm) Standard Error 0.50	0.61 beats per minute (bpm) Standard Error 0.50	-0.91 beats per minute (bpm) Standard Error 0.51

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 weeks

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

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

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure DBP, 26 weeks (n=257, 261, 245)	-0.16 milliliter of mercury (mmHG) Standard Error 0.49	-0.17 milliliter of mercury (mmHG) Standard Error 0.48	-0.29 milliliter of mercury (mmHG) Standard Error 0.50
Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure SBP, 26 weeks (n=257, 261, 245)	-1.28 milliliter of mercury (mmHG) Standard Error 0.78	-1.60 milliliter of mercury (mmHG) Standard Error 0.78	-0.03 milliliter of mercury (mmHG) Standard Error 0.80
Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure SBP, 52 weeks (n=250, 252, 240)	0.17 milliliter of mercury (mmHG) Standard Error 0.81	0.09 milliliter of mercury (mmHG) Standard Error 0.80	0.51 milliliter of mercury (mmHG) Standard Error 0.83
Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure SBP, 78 weeks (n=246, 244, 238)	-0.70 milliliter of mercury (mmHG) Standard Error 0.85	-0.59 milliliter of mercury (mmHG) Standard Error 0.85	0.51 milliliter of mercury (mmHG) Standard Error 0.87
Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure DBP, 52 weeks (n=250, 252, 240)	-0.26 milliliter of mercury (mmHG) Standard Error 0.48	-0.19 milliliter of mercury (mmHG) Standard Error 0.47	-0.93 milliliter of mercury (mmHG) Standard Error 0.49
Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure DBP, 78 weeks (n=246, 244, 238)	-0.44 milliliter of mercury (mmHG) Standard Error 0.52	-0.36 milliliter of mercury (mmHG) Standard Error 0.52	-1.04 milliliter of mercury (mmHG) Standard Error 0.53

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=270 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=271 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=260 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate 26 weeks (n=241, 247, 231)	2.64 beats per minute (bpm) Standard Error 0.539	0.90 beats per minute (bpm) Standard Error 0.529	-1.24 beats per minute (bpm) Standard Error 0.549
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate 52 weeks (n=232, 242, 231)	2.41 beats per minute (bpm) Standard Error 0.564	0.38 beats per minute (bpm) Standard Error 0.551	-1.01 beats per minute (bpm) Standard Error 0.568
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate 78 weeks (n=223, 222, 225)	2.49 beats per minute (bpm) Standard Error 0.592	0.47 beats per minute (bpm) Standard Error 0.588	-0.26 beats per minute (bpm) Standard Error 0.594

SECONDARY outcome

Timeframe: Baseline, 26, 52, and 78 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval QTcF interval, 26 weeks (n=240, 245, 229)	-1.71 milliseconds (msec) Standard Error 0.939	-0.10 milliseconds (msec) Standard Error 0.926	1.24 milliseconds (msec) Standard Error 0.962
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval QTcF interval, 52 weeks (n=231, 240, 228)	1.55 milliseconds (msec) Standard Error 1.074	1.34 milliseconds (msec) Standard Error 1.054	3.70 milliseconds (msec) Standard Error 1.088
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval QTcF interval, 78 weeks (n=221, 220, 222)	1.66 milliseconds (msec) Standard Error 1.045	3.44 milliseconds (msec) Standard Error 1.039	4.44 milliseconds (msec) Standard Error 1.053
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval PR interval, 26 weeks (n=240, 245, 229)	2.78 milliseconds (msec) Standard Error 0.849	2.33 milliseconds (msec) Standard Error 0.836	1.24 milliseconds (msec) Standard Error 0.873
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval PR interval, 52 weeks (n=230, 240, 227)	2.61 milliseconds (msec) Standard Error 0.853	1.88 milliseconds (msec) Standard Error 0.835	1.50 milliseconds (msec) Standard Error 0.868
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval PR interval, 78 weeks (n=221, 220, 222)	2.62 milliseconds (msec) Standard Error 1.034	3.27 milliseconds (msec) Standard Error 1.026	1.21 milliseconds (msec) Standard Error 1.043

SECONDARY outcome

Timeframe: Baseline, 26, 52, 78, and 83 weeks

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

LY2189265 (Dulaglutide) anti-drug antibodies (ADA) were assessed at baseline, 26, 52, and 78 weeks, and at the safety follow-up visit 30 days after study drug discontinuation (83 weeks). The number of participants with initial postbaseline detection of treatment emergent (defined as a 4-fold increase in the ADA titer from baseline) LY2189265 ADA at each time point were summarized.

Outcome measures

Outcome measures
Measure	LY2189265 1.5 mg n=539 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum) 26 weeks	11 participants	—	—
Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum) 52 weeks	3 participants	—	—
Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum) 78 weeks	1 participants	—	—
Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum) 83 weeks	0 participants	—	—

Adverse Events

LY2189265 1.5 mg

Serious events: 32 serious events

Other events: 199 other events

Deaths: 0 deaths

LY2189265 0.75 mg

Serious events: 28 serious events

Other events: 190 other events

Deaths: 0 deaths

Insulin Glargine

Serious events: 33 serious events

Other events: 187 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LY2189265 1.5 mg n=273 participants at risk LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 participants at risk LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 participants at risk Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Injury, poisoning and procedural complications Maternal exposure during pregnancy	0.00% 0/129	0.00% 0/136	0.78% 1/128 • Number of events 1
Blood and lymphatic system disorders Anaemia	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Cardiac disorders Acute coronary syndrome	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Cardiac disorders Acute myocardial infarction	0.00% 0/273	0.74% 2/272 • Number of events 2	0.00% 0/262
Cardiac disorders Angina pectoris	0.37% 1/273 • Number of events 1	0.37% 1/272 • Number of events 1	0.38% 1/262 • Number of events 1
Cardiac disorders Angina unstable	0.00% 0/273	0.74% 2/272 • Number of events 2	0.00% 0/262
Cardiac disorders Atrioventricular block second degree	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Cardiac disorders Cardiac failure	0.37% 1/273 • Number of events 1	0.74% 2/272 • Number of events 2	0.38% 1/262 • Number of events 1
Cardiac disorders Coronary artery disease	0.37% 1/273 • Number of events 1	0.00% 0/272	0.76% 2/262 • Number of events 2
Cardiac disorders Myocardial infarction	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Cardiac disorders Ventricular tachycardia	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Eye disorders Cataract	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Eye disorders Macular fibrosis	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Gastrointestinal disorders Abdominal pain	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Gastrointestinal disorders Faecaloma	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Gastrointestinal disorders Inguinal hernia	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Gastrointestinal disorders Pancreatitis	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
General disorders Chest pain	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
General disorders Fatigue	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
General disorders Sudden death	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Hepatobiliary disorders Cholelithiasis	0.37% 1/273 • Number of events 1	0.37% 1/272 • Number of events 1	0.76% 2/262 • Number of events 2
Hepatobiliary disorders Nodular regenerative hyperplasia	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Infections and infestations Anal abscess	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Infections and infestations Bronchopneumonia	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Infections and infestations Diabetic foot infection	0.37% 1/273 • Number of events 1	0.00% 0/272	0.38% 1/262 • Number of events 1
Infections and infestations Gangrene	0.00% 0/273	0.37% 1/272 • Number of events 1	0.38% 1/262 • Number of events 1
Infections and infestations Gastroenteritis	0.73% 2/273 • Number of events 2	0.00% 0/272	0.00% 0/262
Infections and infestations Hepatitis e	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Infections and infestations Localised infection	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Infections and infestations Lower respiratory tract infection	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Infections and infestations Mastoiditis	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Infections and infestations Osteomyelitis	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Infections and infestations Pneumonia	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Injury, poisoning and procedural complications Fall	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Injury, poisoning and procedural complications Lower limb fracture	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Injury, poisoning and procedural complications Meniscus lesion	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Injury, poisoning and procedural complications Overdose	1.1% 3/273 • Number of events 3	0.00% 0/272	0.00% 0/262
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 2
Injury, poisoning and procedural complications Skeletal injury	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Injury, poisoning and procedural complications Tendon rupture	0.37% 1/273 • Number of events 1	0.00% 0/272	0.38% 1/262 • Number of events 1
Investigations Blood pressure increased	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Investigations Pancreatic enzymes increased	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Metabolism and nutrition disorders Dehydration	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Metabolism and nutrition disorders Hyperglycaemia	1.1% 3/273 • Number of events 3	0.00% 0/272	0.00% 0/262
Metabolism and nutrition disorders Hypoglycaemia	0.73% 2/273 • Number of events 2	0.00% 0/272	0.76% 2/262 • Number of events 2
Metabolism and nutrition disorders Metabolic syndrome	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder papilloma	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/273	0.00% 0/272	0.76% 2/262 • Number of events 2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple myeloma	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	0.00% 0/129	0.74% 1/136 • Number of events 1	0.00% 0/128
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer stage 0	0.69% 1/144 • Number of events 1	0.00% 0/136	0.00% 0/134
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Testicular seminoma (pure)	0.00% 0/144	0.74% 1/136 • Number of events 1	0.00% 0/134
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/129	0.00% 0/136	0.78% 1/128 • Number of events 1
Nervous system disorders Carotid artery stenosis	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Nervous system disorders Cerebral ischaemia	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Nervous system disorders Haemorrhagic stroke	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Nervous system disorders Ischaemic stroke	0.37% 1/273 • Number of events 2	0.00% 0/272	0.38% 1/262 • Number of events 1
Nervous system disorders Sciatica	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Nervous system disorders Spinal cord compression	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Nervous system disorders Spinal cord ischaemia	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Nervous system disorders Syncope	0.37% 1/273 • Number of events 1	0.00% 0/272	0.38% 1/262 • Number of events 1
Nervous system disorders Transient ischaemic attack	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Renal and urinary disorders Calculus ureteric	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Renal and urinary disorders Hydronephrosis	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Renal and urinary disorders Nephrolithiasis	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Renal and urinary disorders Renal failure chronic	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Renal and urinary disorders Ureteric stenosis	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/273	0.00% 0/272	0.38% 1/262 • Number of events 1
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Surgical and medical procedures Cholecystectomy	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Surgical and medical procedures Coronary arterial stent insertion	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Surgical and medical procedures Knee arthroplasty	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Surgical and medical procedures Meniscus removal	0.37% 1/273 • Number of events 1	0.00% 0/272	0.00% 0/262
Vascular disorders Femoral arterial stenosis	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262
Vascular disorders Thrombophlebitis	0.00% 0/273	0.37% 1/272 • Number of events 1	0.00% 0/262

Other adverse events

Other adverse events
Measure	LY2189265 1.5 mg n=273 participants at risk LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 participants at risk LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 participants at risk Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Gastrointestinal disorders Abdominal pain	4.4% 12/273 • Number of events 14	1.1% 3/272 • Number of events 3	1.9% 5/262 • Number of events 5
Gastrointestinal disorders Abdominal pain upper	5.1% 14/273 • Number of events 17	3.3% 9/272 • Number of events 11	0.76% 2/262 • Number of events 2
Gastrointestinal disorders Constipation	4.4% 12/273 • Number of events 12	1.1% 3/272 • Number of events 3	1.1% 3/262 • Number of events 3
Gastrointestinal disorders Diarrhoea	10.6% 29/273 • Number of events 44	9.6% 26/272 • Number of events 36	5.7% 15/262 • Number of events 20
Gastrointestinal disorders Dyspepsia	7.0% 19/273 • Number of events 20	3.3% 9/272 • Number of events 10	2.3% 6/262 • Number of events 22
Gastrointestinal disorders Nausea	15.4% 42/273 • Number of events 56	8.1% 22/272 • Number of events 33	1.5% 4/262 • Number of events 4
Gastrointestinal disorders Vomiting	6.6% 18/273 • Number of events 23	3.7% 10/272 • Number of events 19	1.1% 3/262 • Number of events 3
Infections and infestations Bronchitis	3.3% 9/273 • Number of events 10	2.6% 7/272 • Number of events 8	5.3% 14/262 • Number of events 19
Infections and infestations Influenza	4.4% 12/273 • Number of events 13	4.8% 13/272 • Number of events 16	5.3% 14/262 • Number of events 17
Infections and infestations Nasopharyngitis	5.9% 16/273 • Number of events 21	4.4% 12/272 • Number of events 16	9.2% 24/262 • Number of events 27
Infections and infestations Upper respiratory tract infection	5.5% 15/273 • Number of events 21	4.0% 11/272 • Number of events 18	6.5% 17/262 • Number of events 22
Infections and infestations Urinary tract infection	4.4% 12/273 • Number of events 19	6.2% 17/272 • Number of events 24	5.7% 15/262 • Number of events 18
Infections and infestations Viral infection	1.5% 4/273 • Number of events 4	1.5% 4/272 • Number of events 4	3.1% 8/262 • Number of events 11
Investigations Pancreatic enzymes increased	4.8% 13/273 • Number of events 28	3.3% 9/272 • Number of events 11	1.5% 4/262 • Number of events 7
Metabolism and nutrition disorders Decreased appetite	3.7% 10/273 • Number of events 10	4.4% 12/272 • Number of events 14	0.38% 1/262 • Number of events 1
Metabolism and nutrition disorders Dyslipidaemia	3.3% 9/273 • Number of events 9	2.9% 8/272 • Number of events 8	1.5% 4/262 • Number of events 4
Musculoskeletal and connective tissue disorders Arthralgia	1.1% 3/273 • Number of events 3	2.9% 8/272 • Number of events 9	4.6% 12/262 • Number of events 14
Musculoskeletal and connective tissue disorders Back pain	1.8% 5/273 • Number of events 5	4.0% 11/272 • Number of events 11	3.1% 8/262 • Number of events 10
Musculoskeletal and connective tissue disorders Pain in extremity	4.4% 12/273 • Number of events 12	3.7% 10/272 • Number of events 11	1.1% 3/262 • Number of events 3
Nervous system disorders Dizziness	3.3% 9/273 • Number of events 9	0.74% 2/272 • Number of events 2	1.9% 5/262 • Number of events 5
Nervous system disorders Headache	8.1% 22/273 • Number of events 38	3.3% 9/272 • Number of events 9	5.0% 13/262 • Number of events 20
Respiratory, thoracic and mediastinal disorders Cough	3.3% 9/273 • Number of events 11	2.9% 8/272 • Number of events 8	2.3% 6/262 • Number of events 7
Vascular disorders Hypertension	4.4% 12/273 • Number of events 12	4.8% 13/272 • Number of events 13	4.2% 11/262 • Number of events 11

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	LY2189265 1.5 mg n=273 Participants LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	LY2189265 0.75 mg n=272 Participants LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks	Insulin Glargine n=262 Participants Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Severe HE, 26 weeks	0.01 events per participant per year Standard Deviation 0.12	0.00 events per participant per year Standard Deviation 0.00	0.01 events per participant per year Standard Deviation 0.12
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Severe HE, 52 weeks	0.00 events per participant per year Standard Deviation 0.06	0.00 events per participant per year Standard Deviation 0.00	0.01 events per participant per year Standard Deviation 0.09
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Documented symptomatic HE, 26 weeks	2.35 events per participant per year Standard Deviation 5.41	2.52 events per participant per year Standard Deviation 6.42	3.64 events per participant per year Standard Deviation 6.63
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Documented symptomatic HE, 52 weeks	2.03 events per participant per year Standard Deviation 4.16	1.97 events per participant per year Standard Deviation 5.31	3.34 events per participant per year Standard Deviation 5.91
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Nocturnal HE, 52 weeks	0.90 events per participant per year Standard Deviation 3.13	0.65 events per participant per year Standard Deviation 2.65	2.07 events per participant per year Standard Deviation 4.67
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Nocturnal HE, 78 weeks	0.77 events per participant per year Standard Deviation 2.97	0.59 events per participant per year Standard Deviation 2.47	1.81 events per participant per year Standard Deviation 4.12
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Severe HE, 78 weeks	0.01 events per participant per year Standard Deviation 0.06	0.00 events per participant per year Standard Deviation 0.00	0.01 events per participant per year Standard Deviation 0.06
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Documented symptomatic HE, 78 weeks	1.67 events per participant per year Standard Deviation 3.58	1.66 events per participant per year Standard Deviation 4.96	3.03 events per participant per year Standard Deviation 5.63
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Asymptomatic HE, 26 weeks	3.79 events per participant per year Standard Deviation 8.01	3.58 events per participant per year Standard Deviation 7.70	4.82 events per participant per year Standard Deviation 11.43
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Asymptomatic HE, 52 weeks	3.08 events per participant per year Standard Deviation 6.97	2.68 events per participant per year Standard Deviation 5.40	4.41 events per participant per year Standard Deviation 8.72
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Asymptomatic HE, 78 weeks	2.56 events per participant per year Standard Deviation 5.90	2.38 events per participant per year Standard Deviation 4.95	3.80 events per participant per year Standard Deviation 7.24
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Nocturnal HE, 26 weeks	1.23 events per participant per year Standard Deviation 3.84	0.96 events per participant per year Standard Deviation 3.53	1.86 events per participant per year Standard Deviation 4.84
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Probable symptomatic HE, 26 weeks	0.08 events per participant per year Standard Deviation 0.59	0.14 events per participant per year Standard Deviation 1.39	0.15 events per participant per year Standard Deviation 0.87
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Probable symptomatic HE, 52 weeks	0.07 events per participant per year Standard Deviation 0.40	0.09 events per participant per year Standard Deviation 0.99	0.08 events per participant per year Standard Deviation 0.47
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks Probable symptomatic HE, 78 weeks	0.05 events per participant per year Standard Deviation 0.32	0.07 events per participant per year Standard Deviation 0.67	0.07 events per participant per year Standard Deviation 0.37