AWARD-6: A Study Comparing the Effect of Dulaglutide With Liraglutide in Type 2 Diabetes

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01624259
• Collaborator: (none)
• Enrollment: 599
• Locations: 57
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 10.5
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the benefits and risks of once-weekly dulaglutide compared to once-daily liraglutide in participants with type 2 diabetes who have inadequate glycemic control on metformin.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: LY2189265; Drug: Liraglutide; Drug: Metformin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 599 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Parallel-Arm Study Comparing the Effect of Once-Weekly Dulaglutide With Once-Daily Liraglutide in Patients With Type 2 Diabetes (AWARD-6: Assessment of Weekly AdministRation of LY2189265 in Diabetes-6)
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1.5 mg LY2189265 LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 mg/day, oral, for 26 weeks	Drug: LY2189265; Administered SC; Other Names: Dulaglutide ; Drug: Metformin
Active Comparator: Liraglutide Liraglutide 0.6 mg, SC, once daily for 7 days, then titrated up to Liraglutide 1.2 mg, SC, once daily for 7 days, then titrated up to Liraglutide 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, oral, for 26 weeks	Drug: Liraglutide; Administered SC; Drug: Metformin

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to 26 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) [Baseline, 26 Weeks]

   Least Squares (LS) means of the glycosylated hemoglobin A1c (HbA1c) change from baseline to the primary endpoint at Week 26 was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect, and baseline HbA1c as covariates, via a mixed-effects model for repeated measures (MMRM) analysis using restricted maximum likelihood (REML).

Secondary Outcome Measures

1. Change From Baseline in Body Weight at 26 Weeks [Baseline, Up to 26 Weeks]

   LS means of the weight change from baseline to primary endpoint at Week 26 were calculated using analysis of covariance (ANCOVA) with HbA1c Strata, country, and treatment as fixed effects and baseline body weight as a covariate.

2. Change From Baseline in Body Mass Index (BMI) at 26 Weeks [Baseline, Up to 26 Weeks]

   BMI is an estimate of body fat based on body weight divided by height squared. LS means of the BMI change from baseline to primary endpoint at Week 26 were calculated using ANCOVA with HbA1c Strata, country, and treatment as fixed effects and baseline BMI as a covariate.

3. Change From Baseline in Fasting Plasma Glucose (FPG) at 26 Weeks [Baseline, Up to 26 Weeks]

   LS means of the FPG from baseline to primary endpoint at Week 26 were adjusted by fixed effects of treatment, country, baseline HbA1c strata, and baseline FPG as covariates, via ANCOVA with LOCF.

4. Change From Baseline in 7-Point Self Monitored Plasma Glucose (SMPG) at 26 Weeks [Baseline, 26 Weeks]

   The SMPG data were collected at the following 7 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; and bedtime. The mean of the 7 time points (Daily Mean) was also calculated. LS means of the SMPG change from baseline to primary endpoint at Week 26 were adjusted by fixed effects of treatment, HbA1c strata, country, visit, treatment-by-visit interaction, participant as random effect and baseline SMPG as a covariate, via a MMRM analysis using REML.

5. Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) ≤6.5% or <7% at 26 Weeks [Up to 26 Weeks]

   The percentage of participants who achieved the target HbA1c values at the primary endpoint were analyzed with a repeated logistic regression model (the generalized estimation equation [GEE] model). The model includes pooled country, treatment, visit, treatment-by-visit interaction, and baseline HbA1c as continuous covariates.

6. Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β)- Cell Function (HOMA2-%B) at 26 Weeks [Baseline, Up to 26 Weeks]

   The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-%B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. LS means of the HOMA2-%B change from baseline to primary endpoint at Week 26 was adjusted by fixed effects of treatment, country, baseline HbA1c strata, and baseline HOMA2-%B value as covariate, via an ANCOVA analysis using LOCF.

7. Number of Participants With Reported and Adjudicated Cardiovascular Events [Baseline up to 26 Weeks]

   Deaths and nonfatal cardiovascular (CV) adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal CV 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 reported CV events, number of participants with nonfatal CV events confirmed by adjudication, and number of deaths confirmed by adjudication are summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

8. Change From Baseline in Electrocardiogram (ECG) Parameters, Heart Rate (HR) at 26 Weeks [Baseline, Up to 26 Weeks]

   ECG HR was measured. LS means of change from baseline were analyzed using ANCOVA with HbA1c strata, country, and treatment as fixed effects and baseline HR as a covariate.

9. Change From Baseline in Electrocardiogram (ECG) Parameters PR and QTcF (Fridericia's) Intervals at 26 Weeks [Baseline, 26 Weeks]

   The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. QTcF is the measure of the time between the start of the Q wave and the end of the T wave adjusted using Fridericia's formula. PR is the interval between the P wave and the QRS complex. These parameters were calculated from electrocardiogram (ECG) data. LS means of change from baseline for the PR and QTcF intervals will be analyzed using the MMRM similar to MMRM model for primary outcome, using corresponding baseline and HbA1c strata. Only ECGs obtained at scheduled visits will be used in these summaries and analyses.

10. Change From Baseline in Heart Rate (HR) at 26 Weeks [Baseline, 26 Weeks]

    Descriptive statistics for the actual measurements and LS means of change from baseline for HR (sitting) by treatment arm were analyzed using the MMRM model with treatment, country, visit, and treatment-by-visit interaction as fixed effects, baseline rate as a covariate, and participant as a random effect.

11. Change From Baseline in Blood Pressure (BP) at 26 Weeks [Baseline, 26 Weeks]

    Descriptive statistics for the actual measurements and change from baseline for sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. LS means of change from baseline were calculated using MMRM with treatment, country, visit, and treatment-by-visit interaction as fixed effects, baseline BP as a covariate, and participant as a random effect.

12. Number of Participants With Adjudicated Acute Pancreatitis Events [Baseline up to 30 Weeks]

    The number of participants with events of pancreatitis confirmed by adjudication were summarized cumulatively at 26 weeks (including a 30-day follow up). Pancreatitis events were adjudicated by a committee of physicians external to the Sponsor. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

13. Change From Baseline in Calcitonin at 26 Weeks [Baseline, Up to 26 Weeks]

    A summary of participants having changes in calcitonin values from baseline to primary endpoint of 26 weeks is presented.

14. Change From Baseline in Lipase at 26 Weeks [Baseline, Up to 26 Weeks]

    A summary of participants having changes in lipase evaluation from baseline to primary endpoint of 26 weeks is presented.

15. Change From Baseline in Amylase at 26 Weeks [Baseline, Up to 26 Weeks]

    A summary of participants having changes in amylase evaluation from baseline to primary endpoint of 26 weeks is presented.

16. Percentage of Participants With Self-Reported Hypoglycemia Events [Baseline through 26 Weeks]

    Hypoglycemic events (HE) were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a plasma glucose [PG] concentration of ≤70 mg/dL), asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL), nocturnal (events that occurred between bedtime and waking), or probable symptomatic (events during which symptoms of hypoglycemia were not accompanied by a PG determination but that was presumably caused by a PG of ≤70 mg/dL). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

17. Percentage of Participants Requiring Additional Intervention for Severe, Persistent Hyperglycemia [Baseline through 26 Weeks]

    An additional intervention (rescue therapy) was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation.

18. Rate of Hypoglycemic Events Adjusted Per 30 Days [Baseline through 26 Weeks]

    HE were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a PG concentration of ≤70 mg/dL), asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL), nocturnal (events that occurred between bedtime and waking), or probable symptomatic (events during which symptoms of hypoglycemia were not accompanied by a PG determination but that was presumably caused by a PG of ≤70 mg/dL). The hypoglycemia rate per 30 days was calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period*30 days. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

19. Time to Initiation of Additional Intervention for Severe, Persistent Hyperglycemia [Baseline through 26 Weeks]

    An additional intervention (rescue therapy) was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period.

20. Number of Participants With Allergic or Hypersensitivity Reactions [Baseline through 26 Weeks]

    Allergic and hypersensitivity reactions that were considered possibly related to study drug by the investigator are presented. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module.

21. Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks and 4 Weeks After Last Dose [Baseline up to 4 Weeks Post Last Dose of Study Drug]

    LY2189265 (dulaglutide) anti-drug antibodies (ADA) were assessed at baseline, 26 weeks, and at the safety follow-up visit 4 weeks after study drug discontinuation in dulaglutide-treated participants. A participant was considered to have treatment emergent LY2189265 ADA if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. The number of participants with treatment-emergent LY2189265 ADA from postbaseline to follow up were summarized.

22. Percent Change From Baseline in Lipid Parameters at 26 Weeks [Baseline, Up to 26 Weeks]

    A summary of percent change in lipid parameters (total cholesterol, high-density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], very low-density lipoprotein cholesterol [VLDL], and triglycerides) from baseline to primary endpoint of 26 weeks is presented. LS means of the lipid parameter from baseline to primary endpoint at Week 26 were adjusted by fixed effects of treatment, country, baseline HbA1c strata, and lipid parameter baseline as covariates, via ANCOVA with LOCF.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes

• Not optimally controlled on diet and exercise and a dose of metformin that is at least 1500 milligrams/day (mg/day) and has been at a stable dose for at least 3 months prior to the first study visit

• Glycosylated hemoglobin (HbA1c) greater than or equal to 7.0% and less than or equal to 10.0%

• Accept continued treatment with metformin throughout the trial, as required per protocol

• Men and nonpregnant women aged greater than or equal to 18 years

• Stable weight (plus or minus 5%) greater than or equal to 3 months prior to screening

• Body Mass Index (BMI) less than or equal to 45 kilograms/square meter (kg/m^2)

Exclusion Criteria:

• Have type 1 diabetes mellitus

• Have been treated with ANY other antihyperglycemic medications (other than metformin) at the time of the first study visit or within the 3 months prior to the first study visit

• Have used insulin therapy (outside of pregnancy) any time in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 weeks; any insulin use within 3 months prior to the first study visit

• Have been treated with drugs that promote weight loss within 3 months of the first study visit

• Are receiving chronic (greater than 14 days) systemic glucocorticoid therapy or have received such therapy within the 4 weeks immediately prior to the first study visit

• Have had any of the following cardiovascular conditions within 2 months prior to the first study visit: acute myocardial infarction, New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident

• Have a known clinically significant gastric emptying abnormality (such as, severe diabetic gastroparesis or gastric outlet obstruction) or have undergone gastric bypass (bariatric) surgery or restrictive bariatric surgery

• Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or alanine transaminase level greater than or equal to 3 times the upper limit of normal

• Have a history of chronic pancreatitis or acute idiopathic pancreatitis or were diagnosed with any type of acute pancreatitis within the 3 month period prior to the first study visit

• Have a serum creatinine greater than or equal to 1.5 milligrams/deciliter (mg/dL) (male) or greater than or equal to 1.4 mg/dL (female), or a creatinine clearance less than 60 milliliters/minute (mL/minute)

• Have any self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B, respectively) in the absence of known C-cell hyperplasia (this exclusion includes those participants with a family history of MEN 2A or 2B whose family history for the syndrome is Rearranged during Transfection (RET) negative; the only exception for this exclusion will be for participants whose family members with MEN 2A or 2B have a known RET mutation and the potential participant for the study is negative for that RET mutation)

• Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, or carcinoma (including sporadic, familial, or part of MEN 2A or 2B syndrome)

• Have a serum calcitonin greater than or equal to 20 picograms/milliliter (pg/mL)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Phoenix	Arizona	United States	85027
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chino	California	United States	91710
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fresno	California	United States	93720
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Los Angeles	California	United States	90057
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Spring Valley	California	United States	91978
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fort Lauderdale	Florida	United States	33316
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Miami	Florida	United States	33175
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oviedo	Florida	United States	32765
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Topeka	Kansas	United States	66606
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Louisville	Kentucky	United States	40218
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Shreveport	Louisiana	United States	71101
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Royal Oak	Michigan	United States	48073
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Las Vegas	Nevada	United States	89119
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Perrysburg	Ohio	United States	43551
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kingsport	Tennessee	United States	37660
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dallas	Texas	United States	75230
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hurst	Texas	United States	76054
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	San Antonio	Texas	United States	78228
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Prague		Czech Republic	181 00
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dresden		Germany	01307
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hohenmölsen		Germany	06679
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lingen		Germany	49808
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mainz		Germany	55116
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Neunkirchen		Germany	66539
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	St. Ingbert-Oberwürzbach		Germany	66386
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sulzbach		Germany	92237
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Budapest		Hungary	H-1139
28	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Debrecen		Hungary	4043
29	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dombovar		Hungary	7200
30	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Szekesfehervar		Hungary	8000
31	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monterrey		Mexico	64620
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bialystok		Poland	15-445
33	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gdansk		Poland	80-546
34	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kamieniec Zabkowicki		Poland	57-230
35	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lodz		Poland	90-242
36	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Poznan		Poland	61-853
37	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ruda Slaska		Poland	41-709
38	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Szczecin		Poland	70-506
39	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tychy		Poland	43-100
40	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wroclaw		Poland	50-306
41	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hato Rey		Puerto Rico	00917
42	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rio Grande		Puerto Rico	00745
43	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bucharest		Romania	020045
44	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Galati		Romania	800098
45	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ploiesti		Romania	100342
46	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sibiu		Romania	550371
47	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kosice		Slovakia	04012
48	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Malacky		Slovakia	90101
49	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nitra		Slovakia	94901
50	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nove Mesto Nad Vahom		Slovakia	91501
51	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Alcira		Spain	46600
52	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Alicante		Spain	03114
53	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona		Spain	08022
54	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Centelles		Spain	08540
55	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Málaga		Spain	29006
56	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Palma De Mallorca		Spain	07014
57	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Petrer		Spain	03610

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM-5 PM Eastern time (UTC/GMT-5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01624259
• Other Study ID Numbers: 11377; H9X-MC-GBDE; 2011-003810-18
• First Posted: Jun 20, 2012
• Last Update Posted: Oct 9, 2014
• Last Verified: Oct 1, 2014

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Liraglutide; Dulaglutide

Study Results

Participant Flow

Arm/Group Title	LY2189265	Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 mg/day, oral, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, oral, for 26 weeks
Period Title: Overall Study
STARTED	299	300
Received at Least One Dose of Study Drug	299	300
COMPLETED	269	269
NOT COMPLETED	30	31

Baseline Characteristics

Arm/Group Title	LY2189265	Liraglutide	Total
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, oral, for 26 weeks	Liraglutide 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, oral, for 26 weeks	Total of all reporting groups
Overall Participants	299	300	599
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.49 (9.34)	56.81 (9.91)	56.65 (9.63)
Sex: Female, Male (Count of Participants)
Female	161 53.8%	151 50.3%	312 52.1%
Male	138 46.2%	149 49.7%	287 47.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	75 25.1%	72 24%	147 24.5%
Not Hispanic or Latino	221 73.9%	223 74.3%	444 74.1%
Unknown or Not Reported	3 1%	5 1.7%	8 1.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	20 6.7%	23 7.7%	43 7.2%
Asian	1 0.3%	0 0%	1 0.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	21 7%	16 5.3%	37 6.2%
White	256 85.6%	259 86.3%	515 86%
More than one race	1 0.3%	2 0.7%	3 0.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	97 32.4%	97 32.3%	194 32.4%
Czech Republic	27 9%	28 9.3%	55 9.2%
Hungary	21 7%	19 6.3%	40 6.7%
Mexico	20 6.7%	21 7%	41 6.8%
Slovakia	20 6.7%	22 7.3%	42 7%
Puerto Rico	3 1%	4 1.3%	7 1.2%
Poland	39 13%	42 14%	81 13.5%
Spain	24 8%	24 8%	48 8%
Romania	20 6.7%	17 5.7%	37 6.2%
Germany	28 9.4%	26 8.7%	54 9%
Body Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	93.82 (18.23)	94.35 (18.96)	94.09 (18.58)
Body Mass Index (BMI) (kilograms per meter squared (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meter squared (kg/m^2)]	33.50 (5.07)	33.62 (5.16)	33.56 (5.11)
Glycosylated hemoglobin (HbA1c) (percentage of glycosylated hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated hemoglobin]	8.06 (0.81)	8.05 (0.79)	8.05 (0.80)
Duration of diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.13 (5.41)	7.28 (5.41)	7.21 (5.41)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 26 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
Description	Least Squares (LS) means of the glycosylated hemoglobin A1c (HbA1c) change from baseline to the primary endpoint at Week 26 was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect, and baseline HbA1c as covariates, via a mixed-effects model for repeated measures (MMRM) analysis using restricted maximum likelihood (REML).
Time Frame	Baseline, 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or Liraglutide with evaluable HbA1c data

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	279	272
Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]	-1.42 (0.05)	-1.36 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1.5 mg LY2189265, 1.8 mg Liraglutide
	Comments	To show noninferiority of 1.5 mg LY2189265 relative to 1.8 mg liraglutide with 90% power, 222 completers (444 total) at 26 weeks were required. Noninferiority of 1.5 mg LY2189265 relative to 1.8 mg liraglutide was demonstrated if the upper bound of the two-sided 95% Confidence Interval (CI) for the difference in mean change in HbA1c between the 1.5 mg LY2189265 arm and 1.8 mg liraglutide arm was below 0.4%.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Family-wise Type I error rate was controlled by applying a serial gatekeeping strategy. This calculation assumed a 0 difference in HbA1c between the 1.5 mg LY2189265 1.5-mg arm and 1.8 mg liraglutide, 0.4% margin of noninferiority, common Standard Deviation (SD) of 1.3% for change from baseline in HbA1c, 0.05 two-sided significance level, and 25% dropout rate at 26 weeks.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	1-sided raw p-value (no multiplicity adjustment).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1.5 mg LY2189265, 1.8 mg Liraglutide
	Comments	Superiority analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.186
	Comments	1-sided raw p-value (no multiplicity adjustment)
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Body Weight at 26 Weeks
Description	LS means of the weight change from baseline to primary endpoint at Week 26 were calculated using analysis of covariance (ANCOVA) with HbA1c Strata, country, and treatment as fixed effects and baseline body weight as a covariate.
Time Frame	Baseline, Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or Liraglutide with evaluable body weight data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If no data after date of randomization, the endpoint was considered missing.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	299	299
Least Squares Mean (Standard Error) [kilograms (kg)]	-2.90 (0.22)	-3.61 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1.5 mg LY2189265, 1.8 mg Liraglutide
	Comments	Treatment comparison from ANCOVA model at 26 weeks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	No adjustment for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.17 to 1.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Body Mass Index (BMI) at 26 Weeks
Description	BMI is an estimate of body fat based on body weight divided by height squared. LS means of the BMI change from baseline to primary endpoint at Week 26 were calculated using ANCOVA with HbA1c Strata, country, and treatment as fixed effects and baseline BMI as a covariate.
Time Frame	Baseline, Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable BMI data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If no data after date of randomization, the endpoint was considered missing.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	299	299
Least Squares Mean (Standard Error) [kilograms/square meter (kg/m^2)]	-1.05 (0.08)	-1.30 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1.5 mg LY2189265, 1.8 mg Liraglutide
	Comments	Treatment comparison from ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments	No adjustment for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95%; 0.05 to 0.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at 26 Weeks
Description	LS means of the FPG from baseline to primary endpoint at Week 26 were adjusted by fixed effects of treatment, country, baseline HbA1c strata, and baseline FPG as covariates, via ANCOVA with LOCF.
Time Frame	Baseline, Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable FPG data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If no data after date of randomization, the endpoint was considered missing.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	281	277
Least Squares Mean (Standard Error) [milligrams/deciliter (mg/dL)]	-34.81 (2.13)	-34.25 (2.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1.5 mg LY2189265, 1.8 mg Liraglutide
	Comments	Treatment comparison from ANCOVA model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.828
	Comments	No adjustment for multiplicity.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95%; -5.69 to 4.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.61
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in 7-Point Self Monitored Plasma Glucose (SMPG) at 26 Weeks
Description	The SMPG data were collected at the following 7 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; and bedtime. The mean of the 7 time points (Daily Mean) was also calculated. LS means of the SMPG change from baseline to primary endpoint at Week 26 were adjusted by fixed effects of treatment, HbA1c strata, country, visit, treatment-by-visit interaction, participant as random effect and baseline SMPG as a covariate, via a MMRM analysis using REML.
Time Frame	Baseline, 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable 7-Point SMPG data. Only pre-rescue measurements were used.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	248	256
Least Squares Mean (Standard Error) [mg/dL]	-40.76 (1.50)	-38.51 (1.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1.5 mg LY2189265, 1.8 mg Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.228
	Comments	No adjustment for multiplicity.
	Method	Mixed Models Analysis
	Comments	P-value from pairwise comparison of LS means at 26 weeks from REML-based MMRM.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.25
	Confidence Interval	(2-Sided) 95%; -5.91 to 1.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.86
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) ≤6.5% or <7% at 26 Weeks
Description	The percentage of participants who achieved the target HbA1c values at the primary endpoint were analyzed with a repeated logistic regression model (the generalized estimation equation [GEE] model). The model includes pooled country, treatment, visit, treatment-by-visit interaction, and baseline HbA1c as continuous covariates.
Time Frame	Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or Liraglutide with evaluable HbA1c data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	293	293
HbA1c levels ≤6.5%	54.6 18.3%	50.9 17%
HbA1c levels <7.0%	68.3 22.8%	67.9 22.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1.5 mg LY2189265, 1.8 mg Liraglutide
	Comments	Treatment comparison for HbA1c levels ≤6.5%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.322
	Comments	P-value of treatment comparison at Week 26 is from repeated generalized linear mixed model (GLM model).
	Method	Regression, Logistic
	Comments	No adjustment for multiplicity.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1.5 mg LY2189265, 1.8 mg Liraglutide
	Comments	Treatment comparison for HbA1c levels <7.0%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.925
	Comments	No adjustment for multiplicity.
	Method	Regression, Logistic
	Comments	P-value of treatment comparison at Week 26 is from repeated generalized linear mixed model (GLM model).
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β)- Cell Function (HOMA2-%B) at 26 Weeks
Description	The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-%B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. LS means of the HOMA2-%B change from baseline to primary endpoint at Week 26 was adjusted by fixed effects of treatment, country, baseline HbA1c strata, and baseline HOMA2-%B value as covariate, via an ANCOVA analysis using LOCF.
Time Frame	Baseline, Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable HOMA2-%B data. LOCF was used to impute missing postbaseline values. If there was no data after date of randomization, the endpoint was considered missing.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	275	265
Least Squares Mean (Standard Error) [percentage of HOMA2-%B]	37.03 (2.26)	35.59 (2.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1.5 mg LY2189265, 1.8 mg Liraglutide
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.608
	Comments
	Method	ANCOVA
	Comments	No adjustment for multiplicity.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; -4.06 to 6.92
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.79
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants With Reported and Adjudicated Cardiovascular Events
Description	Deaths and nonfatal cardiovascular (CV) adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal CV 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 reported CV events, number of participants with nonfatal CV events confirmed by adjudication, and number of deaths confirmed by adjudication are summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame	Baseline up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable adjudicated CV event data.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	299	300
Any reported CV events	0 0%	3 1%
Any adjudicated nonfatal CV events	0 0%	1 0.3%
Any confirmed adjudicated deaths	0 0%	0 0%

9. Secondary Outcome

Title	Change From Baseline in Electrocardiogram (ECG) Parameters, Heart Rate (HR) at 26 Weeks
Description	ECG HR was measured. LS means of change from baseline were analyzed using ANCOVA with HbA1c strata, country, and treatment as fixed effects and baseline HR as a covariate.
Time Frame	Baseline, Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable ECG heart rate data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	273	284
Least Squares Mean (Standard Error) [beats per minute (bpm)]	1.9 (0.55)	4.1 (0.54)

10. Secondary Outcome

Title	Change From Baseline in Electrocardiogram (ECG) Parameters PR and QTcF (Fridericia's) Intervals at 26 Weeks
Description	The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. QTcF is the measure of the time between the start of the Q wave and the end of the T wave adjusted using Fridericia's formula. PR is the interval between the P wave and the QRS complex. These parameters were calculated from electrocardiogram (ECG) data. LS means of change from baseline for the PR and QTcF intervals will be analyzed using the MMRM similar to MMRM model for primary outcome, using corresponding baseline and HbA1c strata. Only ECGs obtained at scheduled visits will be used in these summaries and analyses.
Time Frame	Baseline, 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or Liraglutide with evaluable ECG PR or QTcF interval data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	273	284
PR interval (n=270, 278)	3.8 (0.81)	3.3 (0.80)
QTcF interval (n=273, 284)	0.39 (0.90)	-0.72 (0.89)

11. Secondary Outcome

Title	Change From Baseline in Heart Rate (HR) at 26 Weeks
Description	Descriptive statistics for the actual measurements and LS means of change from baseline for HR (sitting) by treatment arm were analyzed using the MMRM model with treatment, country, visit, and treatment-by-visit interaction as fixed effects, baseline rate as a covariate, and participant as a random effect.
Time Frame	Baseline, 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable heart rate data.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	288	288
Least Squares Mean (Standard Error) [bpm]	2.37 (0.4)	3.12 (0.4)

12. Secondary Outcome

Title	Change From Baseline in Blood Pressure (BP) at 26 Weeks
Description	Descriptive statistics for the actual measurements and change from baseline for sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. LS means of change from baseline were calculated using MMRM with treatment, country, visit, and treatment-by-visit interaction as fixed effects, baseline BP as a covariate, and participant as a random effect.
Time Frame	Baseline, 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable BP data.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	278	281
Sitting DBP	-0.22 (0.4)	-0.31 (0.4)
Sitting SBP	-3.36 (0.7)	-2.82 (0.7)

13. Secondary Outcome

Title	Number of Participants With Adjudicated Acute Pancreatitis Events
Description	The number of participants with events of pancreatitis confirmed by adjudication were summarized cumulatively at 26 weeks (including a 30-day follow up). Pancreatitis events were adjudicated by a committee of physicians external to the Sponsor. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame	Baseline up to 30 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or Liraglutide with evaluable adverse event data.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	299	300
Number [participants]	0 0%	0 0%

14. Secondary Outcome

Title	Change From Baseline in Calcitonin at 26 Weeks
Description	A summary of participants having changes in calcitonin values from baseline to primary endpoint of 26 weeks is presented.
Time Frame	Baseline, Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable calcitonin laboratory data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	292	294
Median (Inter-Quartile Range) [picograms/milliliter (pcg/mL)]	0.00	0.00

15. Secondary Outcome

Title	Change From Baseline in Lipase at 26 Weeks
Description	A summary of participants having changes in lipase evaluation from baseline to primary endpoint of 26 weeks is presented.
Time Frame	Baseline, Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable lipase laboratory data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	288	289
Median (Inter-Quartile Range) [units/liter (U/L)]	7.0	11.0

16. Secondary Outcome

Title	Change From Baseline in Amylase at 26 Weeks
Description	A summary of participants having changes in amylase evaluation from baseline to primary endpoint of 26 weeks is presented.
Time Frame	Baseline, Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable amylase laboratory data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	287	289
Median (Inter-Quartile Range) [U/L]	7.0	6.0

17. Secondary Outcome

Title	Percentage of Participants With Self-Reported Hypoglycemia Events
Description	Hypoglycemic events (HE) were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a plasma glucose [PG] concentration of ≤70 mg/dL), asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL), nocturnal (events that occurred between bedtime and waking), or probable symptomatic (events during which symptoms of hypoglycemia were not accompanied by a PG determination but that was presumably caused by a PG of ≤70 mg/dL). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame	Baseline through 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable hypoglycemia event data. Only pre-rescue measurements were used.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	299	300
Documented symptomatic HE	2.7 0.9%	2.7 0.9%
Asymptomatic HE	6.7 2.2%	3.3 1.1%
Severe HE	0.0 0%	0.0 0%
Nocturnal HE	1.3 0.4%	2.0 0.7%
Probable symptomatic HE	1.0 0.3%	1.0 0.3%

18. Secondary Outcome

Title	Percentage of Participants Requiring Additional Intervention for Severe, Persistent Hyperglycemia
Description	An additional intervention (rescue therapy) was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation.
Time Frame	Baseline through 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable concomitant medication data.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	299	300
Number [percentage of participants]	0.3 0.1%	1.0 0.3%

19. Secondary Outcome

Title	Rate of Hypoglycemic Events Adjusted Per 30 Days
Description	HE were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a PG concentration of ≤70 mg/dL), asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL), nocturnal (events that occurred between bedtime and waking), or probable symptomatic (events during which symptoms of hypoglycemia were not accompanied by a PG determination but that was presumably caused by a PG of ≤70 mg/dL). The hypoglycemia rate per 30 days was calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period*30 days. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame	Baseline through 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable hypoglycemic episode data. Only pre-rescue measurements were used.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	299	300
Total HE	0.03 (0.12)	0.04 (0.25)
Documented symptomatic HE	0.01 (0.08)	0.02 (0.17)
Asymptomatic HE	0.02 (0.07)	0.01 (0.08)
Severe HE	0.00 (0.00)	0.00 (0.00)
Nocturnal HE	0.01 (0.05)	0.01 (0.10)
Probable symptomatic HE	0.00 (0.02)	0.01 (1.12)

20. Secondary Outcome

Title	Time to Initiation of Additional Intervention for Severe, Persistent Hyperglycemia
Description	An additional intervention (rescue therapy) was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period.
Time Frame	Baseline through 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable concomitant medication data.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	299	300
Median (95% Confidence Interval) [weeks]	NA	NA

21. Secondary Outcome

Title	Number of Participants With Allergic or Hypersensitivity Reactions
Description	Allergic and hypersensitivity reactions that were considered possibly related to study drug by the investigator are presented. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module.
Time Frame	Baseline through 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable adverse event data.

Arm/Group Title	1.5 mg LY2189265	1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	299	300
Number [participants]	1 0.3%	5 1.7%

22. Secondary Outcome

Title	Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks and 4 Weeks After Last Dose
Description	LY2189265 (dulaglutide) anti-drug antibodies (ADA) were assessed at baseline, 26 weeks, and at the safety follow-up visit 4 weeks after study drug discontinuation in dulaglutide-treated participants. A participant was considered to have treatment emergent LY2189265 ADA if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. The number of participants with treatment-emergent LY2189265 ADA from postbaseline to follow up were summarized.
Time Frame	Baseline up to 4 Weeks Post Last Dose of Study Drug

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 with evaluable LY2189265 ADA data.

Arm/Group Title	1.5 mg LY2189265
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
Measure Participants	290
Number [participants]	3 1%

23. Secondary Outcome

Title	Percent Change From Baseline in Lipid Parameters at 26 Weeks
Description	A summary of percent change in lipid parameters (total cholesterol, high-density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], very low-density lipoprotein cholesterol [VLDL], and triglycerides) from baseline to primary endpoint of 26 weeks is presented. LS means of the lipid parameter from baseline to primary endpoint at Week 26 were adjusted by fixed effects of treatment, country, baseline HbA1c strata, and lipid parameter baseline as covariates, via ANCOVA with LOCF.
Time Frame	Baseline, Up to 26 Weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable lipid laboratory data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Arm/Group Title	LY2189265	Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 26 weeks Metformin: at least 1500 mg/day, oral, for 26 weeks	Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, oral, for 26 weeks
Measure Participants	286	284
Total cholesterol (n=286, 284)	-1.64 (1.18)	0.67 (1.18)
HDL-C (n=286, 284)	6.21 (1.02)	6.46 (1.02)
LDL-C (n=276, 276)	-1.09 (2.17)	3.20 (2.15)
VLDL (n=276, 276)	1.56 (2.63)	2.92 (2.60)
Triglycerides (n=286, 284)	0.59 (2.76)	1.35 (2.76)

Adverse Events

Arm/Group Title	1.5 mg LY2189265		1.8 mg Liraglutide
Arm/Group Description	LY2189265 (Dulaglutide): 1.5 mg, SC, once weekly for 26 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks		Liraglutide: 0.6 mg, SC, once daily for 7 days, then titrated up to 1.2 mg, SC, once daily for 7 days, then titrated up to 1.8 mg, SC, once daily for 24 weeks Metformin: at least 1500 mg/day, administered orally, for 26 weeks
All Cause Mortality
	1.5 mg LY2189265		1.8 mg Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1.5 mg LY2189265		1.8 mg Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/299 (1.7%)		11/300 (3.7%)
Cardiac disorders
Angina pectoris	0/299 (0%)	0	1/300 (0.3%)	1
Tachyarrhythmia	0/299 (0%)	0	1/300 (0.3%)	1
Gastrointestinal disorders
Abdominal pain	0/299 (0%)	0	1/300 (0.3%)	1
Hepatobiliary disorders
Cholelithiasis	1/299 (0.3%)	1	0/300 (0%)	0
Infections and infestations
Bronchopneumonia	1/299 (0.3%)	1	0/300 (0%)	0
Pneumonia influenzal	0/299 (0%)	0	1/300 (0.3%)	1
Respiratory tract infection	0/299 (0%)	0	1/300 (0.3%)	1
Vestibular neuronitis	0/299 (0%)	0	1/300 (0.3%)	1
Injury, poisoning and procedural complications
Ankle fracture	1/299 (0.3%)	1	0/300 (0%)	0
Fall	1/299 (0.3%)	1	0/300 (0%)	0
Investigations
Lipase increased	0/299 (0%)	0	1/300 (0.3%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma	1/299 (0.3%)	1	0/300 (0%)	0
Papillary thyroid cancer	0/299 (0%)	0	1/300 (0.3%)	1
Prostate cancer	1/299 (0.3%)	1	0/300 (0%)	0
Nervous system disorders
Epilepsy	1/299 (0.3%)	1	0/300 (0%)	0
Polyneuropathy	0/299 (0%)	0	1/300 (0.3%)	1
Psychiatric disorders
Schizophrenia	1/299 (0.3%)	1	0/300 (0%)	0
Renal and urinary disorders
Hydronephrosis	0/299 (0%)	0	1/300 (0.3%)	1
Renal failure acute	0/299 (0%)	0	1/300 (0.3%)	1
Vascular disorders
Hypertension	0/299 (0%)	0	1/300 (0.3%)	1
Other (Not Including Serious) Adverse Events
	1.5 mg LY2189265		1.8 mg Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	185/299 (61.9%)		186/300 (62%)
Gastrointestinal disorders
Constipation	11/299 (3.7%)	16	17/300 (5.7%)	20
Diarrhoea	36/299 (12%)	56	36/300 (12%)	51
Dyspepsia	24/299 (8%)	36	18/300 (6%)	22
Nausea	61/299 (20.4%)	108	54/300 (18%)	77
Vomiting	21/299 (7%)	24	25/300 (8.3%)	36
Infections and infestations
Nasopharyngitis	23/299 (7.7%)	30	21/300 (7%)	24
Metabolism and nutrition disorders
Decreased appetite	16/299 (5.4%)	16	20/300 (6.7%)	20
Musculoskeletal and connective tissue disorders
Back pain	11/299 (3.7%)	11	15/300 (5%)	27
Nervous system disorders
Headache	22/299 (7.4%)	36	25/300 (8.3%)	35

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.