Clincosm LogoSign in Get a demo

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

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01075282
Collaborator
(none)
810
Enrollment
78
Locations
3
Arms
33
Duration (Months)
10.4
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if LY2189265 is effective in reducing hemoglobin A1c (HbA1c) and safe, as compared to Insulin Glargine in participants with Type 2 Diabetes. Participants must also be taking metformin and glimepiride.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Rescue therapy refers to 1 of 2 types of additional therapy, each given for a different reason: 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 received rescue therapy were included in the analysis population, but only measurements obtained prior to the beginning of rescue therapy were included in specified efficacy analyses.

Study Design

Study Type:
Interventional
Actual Enrollment :
810 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-Label, Parallel-Arm, Noninferiority Comparison of the Effects of Two Doses of LY2189265 and Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes on Stable Doses of Metformin and Glimepiride
Study Start Date :
Feb 1, 2010
Actual Primary Completion Date :
May 1, 2012
Actual Study Completion Date :
Nov 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: LY2189265 1.5 mg

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

Drug: LY2189265
Other Names:
  • Dulaglutide

    • Drug: Metformin

    Drug: Glimepiride
    Experimental: 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

    Drug: LY2189265
    Other Names:
  • Dulaglutide

    • Drug: Metformin

    Drug: Glimepiride
    Active Comparator: 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

    Drug: Insulin Glargine

    Drug: Metformin

    Drug: Glimepiride

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) [Baseline, 52 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.

    Secondary Outcome Measures

    1. Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) [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.

    2. Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks [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.

    3. Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks [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.

    4. 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 [Baseline, 26, 52, and 78 weeks]

      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.

    5. 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) [Baseline, 52, and 78 weeks]

      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.

    6. Change From Baseline to 52 and 78 Weeks in Glucagon Concentration [Baseline, 52, and 78 weeks]

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

    7. Change From Baseline to 26, 52 and 78 Weeks for Body Weight [Baseline, 26, 52, and 78 weeks]

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

    8. Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index [Baseline, 26, 52, and 78 weeks]

      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.

    9. Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension [Baseline, 26, 52, and 78 weeks]

      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.

    10. Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living [Baseline, 26, 52, and 78 weeks]

      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.

    11. Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception [Baseline, 26, 52, and 78 weeks]

      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.

    12. Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey [Baseline, 26, 52, and 78 weeks]

      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.

    13. Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks [26, 52, and 78 weeks]

      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.

    14. Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks [Baseline through 26, 52, and 78 weeks]

      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.

    15. Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks [Baseline through 26, 52, and 78 weeks]

      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.

    16. Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks [26, 52, and 78 weeks]

      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.

    17. Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes [Baseline, 26, 52, and 78 weeks]

      Amylase (total and pancreas-derived) and lipase concentrations were measured.

    18. Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks [Baseline through 26, 52, and 78 weeks]

      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.

    19. Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin [Baseline, 26, 52, and 78 weeks]

    20. Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks [Baseline through 26, 52, and 78 weeks]

      Information on cardiovascular (CV) risk factors was collected at baseline. Data on any new CV event was prospectively collected using a CV event electronic case report form. At prespecified visits, participants were asked about any new CV event. 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.

    21. Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate [Baseline, 26, 52, and 78 weeks]

      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.

    22. Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure [Baseline, 26, 52, and 78 weeks]

      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.

    23. Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate [Baseline, 26, 52, and 78 weeks]

      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.

    24. Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval [Baseline, 26, 52, and 78 weeks]

      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.

    25. Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum) [Baseline, 26, 52, 78, and 83 weeks]

      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.

    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 well controlled on 1, 2, or 3 oral antidiabetic medications (at least one of them must be metformin and/or a sulfonylurea)

    1. Glycosylated hemoglobin (HbA1c) greater than or equal to 7 and less than or equal to 11 if taking 1 oral antidiabetic medication

    2. HbA1c greater than or equal to 7 and less than or equal to 10 if on 2 or 3 oral antidiabetic medications

    • Accept treatment with metformin and glimepiride throughout the study, as per protocol

    • Willing to inject subcutaneous medication once weekly for LY2189265 or once daily for Insulin Glargine.

    • Stable weight for 3 months prior to screening

    • Body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m^2)

    • Females of child bearing potential must test negative for pregnancy at screening by serum pregnancy test and be willing to use a reliable method of birth control during the study and for 1 month following the last dose of study drug

    Exclusion Criteria:

    • Type 1 Diabetes

    • HbA1c equal to or less than 6.5 at randomization

    • Chronic insulin use

    • Taking drugs to promote weight loss by prescription or over the counter

    • Taking systemic steroids for greater than 14 days except for topical, eye, nasal, or inhaled

    • History of Heart Failure New York Heart Classification III or IV, or acute myocardial infarction, or stroke within 2 months of screening

    • Gastrointestinal (GI) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking drugs that directly affect GI motility

    • Hepatitis or liver disease or ALT (alanine transaminase) greater than 3.0 of upper normal limit

    • Acute or chronic pancreatitis of any form

    • Renal disease (kidney) with a serum creatinine of greater than or equal to 1.5 milligrams per deciliter (mg/dL) for males and greater than or equal to 1.4 mg/dL for females, or a creatinine clearance of less than 60 milliliters per minute (ml/min)

    • History (includes family) of type 2A or 2B Multiple Endocrine Neoplasia (MEN 2A or 2B) or medullary c-cell hyperplasia or thyroid cancer

    • A serum calcitonin greater than or equal to 20 picograms per milliliter (pcg/ml) at screening

    • Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis

    • History of or active malignancy except skin or in situ cervical or prostate cancer for within last 5 years

    • Sickle cell, hemolytic anemia, or other hematological condition that may interfere with HbA1c testing

    • Organ transplant except cornea

    • Have enrolled in another clinical trial within the last 30 days

    • Have previously signed an informed consent or participated in a LY2189265 study

    • Have taken a glucagon-like peptide 1 (GLP-1) receptor agonist within the 3 months prior to screening

    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. Buenos Aires Argentina C1425AGC
    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. Caba Argentina C1417EYG
    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. Córdoba Argentina 5006
    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. Mendoza Argentina 5500
    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. Wollongong New South Wales Australia 2500
    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. Brisbane Queensland Australia 4029
    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. Keswick South Australia Australia 5035
    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. East Ringwood Victoria Australia 3135
    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. Heidelberg Victoria Australia 3081
    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. Gribomont Belgium 6887
    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. Halen Belgium 3545
    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. Leuven Belgium 3000
    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. Joinville Brazil 89201-260
    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. São Paulo Brazil 05403-900
    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. Edmonton Alberta Canada T5J 3N4
    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. Coquitlam British Columbia Canada V3K 3P4
    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. Winnipeg Manitoba Canada R3E 3P4
    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. St. John Newfoundland and Labrador Canada A1E 2C2
    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. Markham Ontario Canada L6B 0P9
    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. Mississauga Ontario Canada L5M 2V8
    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. Montreal Quebec Canada H2W 1R7
    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. Sherbrooke Quebec Canada J1G 5K2
    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. Osijek Croatia 31000
    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. Slavonski Brod Croatia 35 000
    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. Zagreb Croatia 10000
    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. Holesov Czech Republic 769 01
    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. Prague Czech Republic 140 59
    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. Corbeil-Essonnes France 91106
    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. Dijon France 21079
    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. Nantes France 44093
    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. Pessac France 33604
    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. Tours France 37044
    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. Athens Greece 11527
    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. Budapest Hungary 1036
    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. Mako Hungary 6900
    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. Mosonmagyarovar Hungary 9200
    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. Szekesfehervar Hungary 8000
    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. Aligarh India 202002
    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. Bangalore India 560003
    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. Chennai India 600029
    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. Indore India 452002
    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. Jaipur India 302001
    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. Mumbai India 400053
    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. Patna India 800 020
    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. Firenze Italy 50141
    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. Milano Italy 20132
    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. Bucheon Korea, Republic of 420-717
    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. Ilsan Korea, Republic of 411706
    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. Pusan Korea, Republic of 614-735
    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. Coatzacoalcos Mexico 96400
    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. Cuernavaca Mexico 62250
    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. Guadalajara Mexico 44656
    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. Monterrey Mexico 64570
    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. Bialystok Poland 15-404
    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. Bydogoszcz Poland 85-094
    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. Krakow Poland 31-261
    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. Szczecin Poland 71-455
    58 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. Warsaw Poland 02-507
    59 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 50-127
    60 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. Baia Mare Romania 430123
    61 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
    62 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 800587
    63 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. Oradea Romania 410025
    64 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 04001
    65 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
    66 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. Avila Spain 05004
    67 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. Palencia Spain 34005
    68 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. Requena Spain 46340
    69 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. Göteborg Sweden 41345
    70 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. Helsingborg Sweden 25187
    71 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. Lund Sweden 22185
    72 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. Stockholm Sweden 11157
    73 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. Chiayi City Taiwan 600
    74 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. Kaohsiung Taiwan 807
    75 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. Tainan Taiwan 70403
    76 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. Taipei Taiwan 11031
    77 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. Tao-Yuan Taiwan 333
    78 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. Yung-Kang, Tainan Taiwan 710

    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:
    NCT01075282
    Other Study ID Numbers:
    • 11374
    • H9X-MC-GBDB
    First Posted:
    Feb 25, 2010
    Last Update Posted:
    Jan 16, 2015
    Last Verified:
    Jan 1, 2015
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Metformin
    Insulin Glargine
    Glimepiride
    Dulaglutide

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Period Title: Overall Study
    STARTED 273 272 265
    Received at Least One Dose of Study Drug 273 272 262
    COMPLETED 242 243 238
    NOT COMPLETED 31 29 27

    Baseline Characteristics

    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine Total
    Arm/Group Description 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 (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: 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 of all reporting groups
    Overall Participants 273 272 262 807
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    56.24
    (9.76)
    56.56
    (9.27)
    57.21
    (9.38)
    56.66
    (9.47)
    Sex: Female, Male (Count of Participants)
    Female
    129
    47.3%
    136
    50%
    128
    48.9%
    393
    48.7%
    Male
    144
    52.7%
    136
    50%
    134
    51.1%
    414
    51.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    98
    35.9%
    96
    35.3%
    97
    37%
    291
    36.1%
    Not Hispanic or Latino
    175
    64.1%
    176
    64.7%
    165
    63%
    516
    63.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    29
    10.6%
    31
    11.4%
    29
    11.1%
    89
    11%
    Asian
    48
    17.6%
    46
    16.9%
    43
    16.4%
    137
    17%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    0.4%
    1
    0.4%
    2
    0.8%
    4
    0.5%
    White
    193
    70.7%
    193
    71%
    184
    70.2%
    570
    70.6%
    More than one race
    2
    0.7%
    1
    0.4%
    4
    1.5%
    7
    0.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    Taiwan
    13
    4.8%
    13
    4.8%
    12
    4.6%
    38
    4.7%
    Slovakia
    1
    0.4%
    1
    0.4%
    0
    0%
    2
    0.2%
    Greece
    6
    2.2%
    6
    2.2%
    7
    2.7%
    19
    2.4%
    Spain
    10
    3.7%
    12
    4.4%
    13
    5%
    35
    4.3%
    Italy
    2
    0.7%
    3
    1.1%
    1
    0.4%
    6
    0.7%
    India
    30
    11%
    27
    9.9%
    27
    10.3%
    84
    10.4%
    France
    2
    0.7%
    3
    1.1%
    1
    0.4%
    6
    0.7%
    Czech Republic
    12
    4.4%
    14
    5.1%
    13
    5%
    39
    4.8%
    Hungary
    16
    5.9%
    16
    5.9%
    15
    5.7%
    47
    5.8%
    Mexico
    29
    10.6%
    28
    10.3%
    27
    10.3%
    84
    10.4%
    Canada
    26
    9.5%
    25
    9.2%
    24
    9.2%
    75
    9.3%
    Argentina
    55
    20.1%
    54
    19.9%
    54
    20.6%
    163
    20.2%
    Belgium
    7
    2.6%
    5
    1.8%
    3
    1.1%
    15
    1.9%
    Brazil
    6
    2.2%
    5
    1.8%
    7
    2.7%
    18
    2.2%
    Poland
    16
    5.9%
    18
    6.6%
    17
    6.5%
    51
    6.3%
    Croatia
    3
    1.1%
    4
    1.5%
    4
    1.5%
    11
    1.4%
    Romania
    23
    8.4%
    22
    8.1%
    22
    8.4%
    67
    8.3%
    Australia
    13
    4.8%
    13
    4.8%
    13
    5%
    39
    4.8%
    Sweden
    2
    0.7%
    0
    0%
    1
    0.4%
    3
    0.4%
    Korea, Republic of
    1
    0.4%
    3
    1.1%
    1
    0.4%
    5
    0.6%
    Body Weight (kilograms) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms]
    85.13
    (17.90)
    86.18
    (18.15)
    87.66
    (19.62)
    86.31
    (18.56)
    Body Mass Index (BMI) (kilograms per square meter (kg/m^2)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms per square meter (kg/m^2)]
    31.23
    (5.21)
    31.51
    (5.41)
    31.91
    (5.76)
    31.55
    (5.46)
    Glycosylated Hemoglobin (HbA1c) (percentage of glycosylated hemoglobin) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage of glycosylated hemoglobin]
    8.18
    (1.03)
    8.13
    (0.98)
    8.10
    (0.95)
    8.14
    (0.99)
    Duration of Diabetes (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    9.13
    (6.22)
    9.28
    (5.93)
    8.87
    (5.98)
    9.10
    (6.04)
    Fasting Serum Glucose (millimoles per liter (mmol/L)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [millimoles per liter (mmol/L)]
    9.16
    (2.73)
    8.96
    (2.70)
    9.08
    (2.66)
    9.07
    (2.69)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
    Description Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.
    Time Frame Baseline, 52 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 263 267 259
    Least Squares Mean (Standard Error) [percentage of glycosylated hemoglobin]
    -1.08
    (0.06)
    -0.76
    (0.06)
    -0.63
    (0.06)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments The study was designed with 90% power to detect non-inferiority of LY2189265 1.5 mg vs insulin glargine on HbA1c change from baseline at the 52-week primary endpoint with a margin of 0.4%, a standard deviation of 1.3%, and a 1-sided alpha of 0.025 assuming no true difference between treatments. This corresponds to 223 participants per arm, with an assumed drop-out rate of 20%.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Family-wise Type I error rate was controlled by applying gatekeeping strategy.
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is adjusted for multiplicity, based on tree-gatekeeping strategy. To determine significance, p-value is compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.45
    Confidence Interval (2-Sided) 95%
    -0.60 to -0.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments Non-inferiority analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Family-wise Type I error rate was controlled by applying gatekeeping strategy.
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is adjusted for multiplicity, based on tree-gatekeeping strategy. To determine significance, p-value is compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.13
    Confidence Interval (2-Sided) 95%
    -0.29 to 0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments Superiority analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is adjusted for multiplicity, based on tree-gatekeeping strategy. To determine significance, p-value is compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.45
    Confidence Interval (2-Sided) 95%
    -0.60 to -0.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments Superiority analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.05
    Comments P-value is adjusted for multiplicity, based on tree-gatekeeping strategy. To determine significance, p-value is compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.13
    Confidence Interval (2-Sided) 95%
    -0.29 to 0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
    Description Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.
    Time Frame Baseline, 26 weeks, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    26 weeks (n=263, 266, 258)
    -1.16
    (0.06)
    -0.89
    (0.05)
    -0.65
    (0.06)
    78 weeks (n=263, 267, 259)
    -0.90
    (0.07)
    -0.62
    (0.07)
    -0.59
    (0.07)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments Non-inferiority analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Family-wise Type I error rate was controlled by applying gatekeeping strategy.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 26 weeks. P-value is adjusted for multiplicity, based on tree-gatekeeping strategy, and compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.51
    Confidence Interval (2-Sided) 95%
    -0.65 to -0.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments Non-inferiority analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Family-wise Type I error rate was controlled by applying gatekeeping strategy.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 26 weeks. P-value is adjusted for multiplicity, based on tree-gatekeeping strategy, and compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.24
    Confidence Interval (2-Sided) 95%
    -0.38 to -0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments Superiority analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 26 weeks. P-value is adjusted for multiplicity, based on tree-gatekeeping strategy, and compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.51
    Confidence Interval (2-Sided) 95%
    -0.65 to -0.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments Superiority analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 26 weeks. P-value is adjusted for multiplicity, based on tree-gatekeeping strategy, and compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.24
    Confidence Interval (2-Sided) 95%
    -0.38 to -0.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments Non-inferiority analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Family-wise Type I error rate was controlled by applying gatekeeping strategy.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 78 weeks. P-value is adjusted for multiplicity, based on tree-gatekeeping strategy, and compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.31
    Confidence Interval (2-Sided) 95%
    -0.50 to -0.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments Non-inferiority analysis.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Family-wise Type I error rate was controlled by applying gatekeeping strategy.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 78 weeks. P-value is adjusted for multiplicity, based on tree-gatekeeping strategy, and compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.03
    Confidence Interval (2-Sided) 95%
    -0.21 to 0.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments Superiority analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 78 weeks. P-value is adjusted for multiplicity, based on tree-gatekeeping strategy, and compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.31
    Confidence Interval (2-Sided) 95%
    -0.50 to -0.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments Superiority analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.378
    Comments Treatment comparison at 78 weeks. P-value is adjusted for multiplicity, based on tree-gatekeeping strategy, and compared to the family-wise 1-sided Type I error of 0.025. The confidence interval is not adjusted for multiplicity.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.03
    Confidence Interval (2-Sided) 95%
    -0.21 to 0.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks
    Description 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.
    Time Frame 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    26 weeks (n=263, 266, 258)
    153
    56%
    122
    44.9%
    84
    32.1%
    52 weeks (n=263, 267, 259)
    140
    51.3%
    99
    36.4%
    80
    30.5%
    78 weeks (n=263, 267, 259)
    129
    47.3%
    91
    33.5%
    79
    30.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 26 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.61
    Confidence Interval (2-Sided) 95%
    2.98 to 7.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 26 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.13
    Confidence Interval (2-Sided) 95%
    1.41 to 3.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 52 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.76
    Confidence Interval (2-Sided) 95%
    2.45 to 5.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.098
    Comments Treatment comparison at 52 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.42
    Confidence Interval (2-Sided) 95%
    0.94 to 2.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 78 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.77
    Confidence Interval (2-Sided) 95%
    1.85 to 4.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.334
    Comments Treatment comparison at 78 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.22
    Confidence Interval (2-Sided) 95%
    0.82 to 1.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks
    Description 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.
    Time Frame 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    26 weeks (n=263, 266, 258)
    97
    35.5%
    74
    27.2%
    40
    15.3%
    52 weeks (n=263, 267, 259)
    71
    26%
    60
    22.1%
    35
    13.4%
    78 weeks (n=263, 267, 259)
    74
    27.1%
    59
    21.7%
    43
    16.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 26 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.70
    Confidence Interval (2-Sided) 95%
    2.90 to 7.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 26 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.54
    Confidence Interval (2-Sided) 95%
    1.57 to 4.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 52 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.97
    Confidence Interval (2-Sided) 95%
    1.81 to 4.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments Treatment comparison at 52 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.07
    Confidence Interval (2-Sided) 95%
    1.26 to 3.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 78 weeks.
    Method Regression, Logistic
    Comments Treatment comparison at 78 weeks.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.27
    Confidence Interval (2-Sided) 95%
    1.44 to 3.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.073
    Comments Treatment comparison at 78 weeks.
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.53
    Confidence Interval (2-Sided) 95%
    0.96 to 2.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title 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
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 231 242 228
    26 weeks (n=199, 204, 190)
    -1.79
    (0.10)
    -1.46
    (0.10)
    -1.58
    (0.10)
    52 weeks (n=180, 185, 176)
    -1.69
    (0.11)
    -1.32
    (0.11)
    -1.44
    (0.11)
    78 weeks (n=172, 164, 168)
    -1.55
    (0.13)
    -1.15
    (0.12)
    -1.47
    (0.13)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.109
    Comments Treatment comparison at 26 weeks.
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.335
    Comments Treatment comparison at 26 weeks.
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.091
    Comments Treatment comparison at 52 weeks.
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.400
    Comments Treatment comparison at 52 weeks.
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.641
    Comments Treatment comparison at 78 weeks.
    Method Mixed Models Analysis
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.055
    Comments Treatment comparison at 78 weeks.
    Method Mixed Models Analysis
    Comments
    6. Secondary Outcome
    Title 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)
    Description 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.
    Time Frame Baseline, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg
    Arm/Group Description 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 (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
    Measure Participants 222 230
    HOMA2-%B, 52 weeks (n=175, 181)
    29.95
    (4.61)
    24.60
    (4.51)
    HOMA2-%B, 78 weeks (n=167, 165)
    28.54
    (4.78)
    15.66
    (4.75)
    HOMA2-%S, 52 weeks (n=175,181)
    -2.89
    (1.21)
    -2.66
    (1.19)
    HOMA2-%S, 78 weeks (n=167, 165)
    -2.64
    (1.23)
    -3.62
    (1.23)
    7. Secondary Outcome
    Title Change From Baseline to 52 and 78 Weeks in Glucagon Concentration
    Description 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.
    Time Frame Baseline, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 235 235 232
    52 weeks (n=232, 231, 228)
    -3.91
    (0.47)
    -3.31
    (0.47)
    -3.85
    (0.47)
    78 weeks (n=235, 235, 232)
    -3.57
    (0.47)
    -3.37
    (0.47)
    -3.65
    (0.47)
    8. Secondary Outcome
    Title Change From Baseline to 26, 52 and 78 Weeks for Body Weight
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 272 270 259
    26 weeks
    -1.82
    (0.20)
    -1.47
    (0.20)
    1.01
    (0.20)
    52 weeks
    -1.87
    (0.24)
    -1.33
    (0.24)
    1.44
    (0.24)
    78 weeks
    -1.96
    (0.26)
    -1.54
    (0.26)
    1.28
    (0.26)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 26 weeks.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 2.83
    Confidence Interval (2-Sided) 95%
    2.33 to 3.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 26 weeks.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 2.48
    Confidence Interval (2-Sided) 95%
    1.99 to 2.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 52 weeks.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 3.31
    Confidence Interval (2-Sided) 95%
    2.71 to 3.90
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 52 weeks.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 2.77
    Confidence Interval (2-Sided) 95%
    2.17 to 3.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection LY2189265 1.5 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 78 weeks.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 3.24
    Confidence Interval (2-Sided) 95%
    2.59 to 3.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection LY2189265 0.75 mg, Insulin Glargine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Treatment comparison at 78 weeks.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 2.82
    Confidence Interval (2-Sided) 95%
    2.17 to 3.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable BMI data.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    26 weeks (n=257, 261, 245)
    -0.64
    (0.07)
    -0.50
    (0.07)
    0.44
    (0.07)
    52 weeks (n=250, 252, 238)
    -0.64
    (0.08)
    -0.39
    (0.08)
    0.62
    (0.08)
    78 weeks (n=246, 244, 238)
    -0.64
    (0.09)
    -0.39
    (0.09)
    0.59
    (0.10)
    10. Secondary Outcome
    Title Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    EQ-5D UK, 26 weeks (n=257, 254, 249)
    0.01
    (0.01)
    0.00
    (0.01)
    -0.01
    (0.01)
    EQ-5D UK, 52 weeks (n=259, 260, 253)
    0.01
    (0.01)
    0.00
    (0.01)
    -0.04
    (0.01)
    EQ-5D UK, 78 weeks (n=259, 260, 253)
    0.01
    (0.01)
    0.00
    (0.01)
    0.00
    (0.01)
    VAS, 26 weeks (n=253, 252, 243)
    3.3
    (0.83)
    3.4
    (0.84)
    0.8
    (0.86)
    VAS, 52 weeks (n=260, 258, 252)
    3.2
    (0.85)
    2.3
    (0.85)
    1.1
    (0.88)
    VAS, 78 weeks (n=260, 258, 252)
    3.8
    (0.85)
    3.2
    (0.85)
    2.2
    (0.89)
    11. Secondary Outcome
    Title Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 260
    26 weeks (n=256, 256, 248)
    0.7
    (0.30)
    0.1
    (0.30)
    -0.3
    (0.30)
    52 weeks (n=260, 261, 249)
    0.9
    (0.31)
    0.4
    (0.31)
    -0.6
    (0.32)
    78 weeks (n=260, 261, 249)
    1.0
    (0.31)
    0.3
    (0.31)
    -0.3
    (0.32)
    12. Secondary Outcome
    Title Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    26 weeks (n=258, 258, 251)
    0.1
    (0.16)
    0.2
    (0.16)
    -0.1
    (0.16)
    52 weeks (n=260, 261, 252)
    0.5
    (0.16)
    0.2
    (0.16)
    0.1
    (0.16)
    78 weeks (n=260, 261, 252)
    0.5
    (0.16)
    0.3
    (0.15)
    0.1
    (0.16)
    13. Secondary Outcome
    Title Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 270 271 255
    26 weeks (n=255, 255, 244)
    -2.8
    (0.95)
    -2.4
    (0.96)
    0.3
    (0.98)
    52 weeks (n=258, 259, 245)
    -4.2
    (0.83)
    -4.1
    (0.83)
    -1.0
    (0.86)
    78 weeks (n=258, 259, 245)
    -4.6
    (0.82)
    -4.7
    (0.82)
    -2.0
    (0.85)
    14. Secondary Outcome
    Title Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks
    Description 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.
    Time Frame 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    26 weeks
    160
    58.6%
    146
    53.7%
    137
    52.3%
    52 weeks
    189
    69.2%
    175
    64.3%
    175
    66.8%
    78 weeks
    201
    73.6%
    188
    69.1%
    192
    73.3%
    15. Secondary Outcome
    Title Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks
    Description 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.
    Time Frame Baseline through 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    Severe HE, 26 weeks
    1
    0
    1
    Severe HE, 52 weeks
    1
    0
    2
    Severe HE, 78 weeks
    2
    0
    2
    Documented symptomatic HE, 26 weeks
    311
    315
    447
    Documented symptomatic HE, 52 weeks
    515
    444
    789
    Documented symptomatic HE, 78 weeks
    607
    515
    1033
    Asymptomatic HE, 26 weeks
    500
    484
    609
    Asymptomatic HE, 52 weeks
    757
    709
    1093
    Asymptomatic HE, 78 weeks
    884
    911
    1358
    Nocturnal HE, 26 weeks
    145
    117
    240
    Nocturnal HE, 52 weeks
    185
    147
    519
    Nocturnal HE, 78 weeks
    215
    184
    635
    Probable symptomatic HE, 26 weeks
    11
    19
    20
    Probable symptomatic HE, 52 weeks
    17
    24
    22
    Probable symptomatic HE, 78 weeks
    20
    28
    26
    16. Secondary Outcome
    Title Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks
    Description 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.
    Time Frame Baseline through 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    Severe HE, 26 weeks
    0.01
    (0.12)
    0.00
    (0.00)
    0.01
    (0.12)
    Severe HE, 52 weeks
    0.00
    (0.06)
    0.00
    (0.00)
    0.01
    (0.09)
    Severe HE, 78 weeks
    0.01
    (0.06)
    0.00
    (0.00)
    0.01
    (0.06)
    Documented symptomatic HE, 26 weeks
    2.35
    (5.41)
    2.52
    (6.42)
    3.64
    (6.63)
    Documented symptomatic HE, 52 weeks
    2.03
    (4.16)
    1.97
    (5.31)
    3.34
    (5.91)
    Documented symptomatic HE, 78 weeks
    1.67
    (3.58)
    1.66
    (4.96)
    3.03
    (5.63)
    Asymptomatic HE, 26 weeks
    3.79
    (8.01)
    3.58
    (7.70)
    4.82
    (11.43)
    Asymptomatic HE, 52 weeks
    3.08
    (6.97)
    2.68
    (5.40)
    4.41
    (8.72)
    Asymptomatic HE, 78 weeks
    2.56
    (5.90)
    2.38
    (4.95)
    3.80
    (7.24)
    Nocturnal HE, 26 weeks
    1.23
    (3.84)
    0.96
    (3.53)
    1.86
    (4.84)
    Nocturnal HE, 52 weeks
    0.90
    (3.13)
    0.65
    (2.65)
    2.07
    (4.67)
    Nocturnal HE, 78 weeks
    0.77
    (2.97)
    0.59
    (2.47)
    1.81
    (4.12)
    Probable symptomatic HE, 26 weeks
    0.08
    (0.59)
    0.14
    (1.39)
    0.15
    (0.87)
    Probable symptomatic HE, 52 weeks
    0.07
    (0.40)
    0.09
    (0.99)
    0.08
    (0.47)
    Probable symptomatic HE, 78 weeks
    0.05
    (0.32)
    0.07
    (0.67)
    0.07
    (0.37)
    17. Secondary Outcome
    Title Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks
    Description 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.
    Time Frame 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    26 weeks
    2
    0.7%
    4
    1.5%
    0
    0%
    52 weeks
    11
    4%
    20
    7.4%
    8
    3.1%
    78 weeks
    24
    8.8%
    34
    12.5%
    16
    6.1%
    18. Secondary Outcome
    Title Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes
    Description Amylase (total and pancreas-derived) and lipase concentrations were measured.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 271 269 259
    Amylase (total), 26 weeks
    4.000
    4.000
    2.000
    Amylase (total), 52 weeks
    4.000
    5.000
    3.000
    Amylase (total), 78 weeks
    4.000
    4.000
    1.000
    Amylase (pancreas-derived), 26 weeks
    3.000
    3.000
    1.000
    Amylase (pancreas-derived), 52 weeks
    3.000
    3.000
    1.000
    Amylase (pancreas-derived), 78 weeks
    2.000
    2.000
    0.000
    Lipase, 26 weeks
    5.000
    5.000
    -1.000
    Lipase, 52 weeks
    4.000
    4.000
    -1.000
    Lipase, 78 weeks
    4.000
    4.000
    -2.000
    19. Secondary Outcome
    Title Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks
    Description 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.
    Time Frame Baseline through 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    26 weeks
    1
    0.4%
    1
    0.4%
    0
    0%
    52 weeks
    2
    0.7%
    1
    0.4%
    0
    0%
    78 weeks
    2
    0.7%
    1
    0.4%
    0
    0%
    20. Secondary Outcome
    Title Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin
    Description
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    26 weeks (n=266, 267, 258)
    0.163
    (1.31)
    0.097
    (1.20)
    0.149
    (1.30)
    52 weeks (n=266, 269, 259)
    0.128
    (1.20)
    0.132
    (1.32)
    0.176
    (1.62)
    78 weeks (n=267, 269, 259)
    0.086
    (1.31)
    0.035
    (1.20)
    0.151
    (1.73)
    21. Secondary Outcome
    Title Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks
    Description 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.
    Time Frame Baseline through 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    Any CV event, 26 weeks
    2
    0.7%
    1
    0.4%
    3
    1.1%
    Any fatal CV event, 26 weeks
    0
    0%
    0
    0%
    0
    0%
    Any non-fatal CV event, 26 weeks
    2
    0.7%
    1
    0.4%
    3
    1.1%
    Any CV event, 52 weeks
    3
    1.1%
    4
    1.5%
    6
    2.3%
    Any fatal CV event, 52 weeks
    0
    0%
    0
    0%
    1
    0.4%
    Any non-fatal CV event, 52 weeks
    3
    1.1%
    4
    1.5%
    5
    1.9%
    Any CV event, 78 week
    3
    1.1%
    6
    2.2%
    9
    3.4%
    Any fatal CV event, 78 week
    0
    0%
    1
    0.4%
    1
    0.4%
    Any non-fatal CV event, 78 week
    3
    1.1%
    6
    2.2%
    8
    3.1%
    22. Secondary Outcome
    Title Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable sitting pulse rate data.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    26 weeks (n=257, 260, 245)
    1.56
    (0.49)
    0.74
    (0.48)
    -1.21
    (0.50)
    52 weeks (n=250, 252, 240)
    1.29
    (0.50)
    0.51
    (0.49)
    -0.52
    (0.51)
    78 weeks (n=246, 244, 238)
    1.31
    (0.50)
    0.61
    (0.50)
    -0.91
    (0.51)
    23. Secondary Outcome
    Title Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable blood pressure data.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    SBP, 26 weeks (n=257, 261, 245)
    -1.28
    (0.78)
    -1.60
    (0.78)
    -0.03
    (0.80)
    SBP, 52 weeks (n=250, 252, 240)
    0.17
    (0.81)
    0.09
    (0.80)
    0.51
    (0.83)
    SBP, 78 weeks (n=246, 244, 238)
    -0.70
    (0.85)
    -0.59
    (0.85)
    0.51
    (0.87)
    DBP, 26 weeks (n=257, 261, 245)
    -0.16
    (0.49)
    -0.17
    (0.48)
    -0.29
    (0.50)
    DBP, 52 weeks (n=250, 252, 240)
    -0.26
    (0.48)
    -0.19
    (0.47)
    -0.93
    (0.49)
    DBP, 78 weeks (n=246, 244, 238)
    -0.44
    (0.52)
    -0.36
    (0.52)
    -1.04
    (0.53)
    24. Secondary Outcome
    Title Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable ECG heart rate data.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 270 271 260
    26 weeks (n=241, 247, 231)
    2.64
    (0.539)
    0.90
    (0.529)
    -1.24
    (0.549)
    52 weeks (n=232, 242, 231)
    2.41
    (0.564)
    0.38
    (0.551)
    -1.01
    (0.568)
    78 weeks (n=223, 222, 225)
    2.49
    (0.592)
    0.47
    (0.588)
    -0.26
    (0.594)
    25. Secondary Outcome
    Title Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
    Description 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.
    Time Frame Baseline, 26, 52, and 78 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable ECG QTcF or PR Interval data.
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    Measure Participants 273 272 262
    QTcF interval, 26 weeks (n=240, 245, 229)
    -1.71
    (0.939)
    -0.10
    (0.926)
    1.24
    (0.962)
    QTcF interval, 52 weeks (n=231, 240, 228)
    1.55
    (1.074)
    1.34
    (1.054)
    3.70
    (1.088)
    QTcF interval, 78 weeks (n=221, 220, 222)
    1.66
    (1.045)
    3.44
    (1.039)
    4.44
    (1.053)
    PR interval, 26 weeks (n=240, 245, 229)
    2.78
    (0.849)
    2.33
    (0.836)
    1.24
    (0.873)
    PR interval, 52 weeks (n=230, 240, 227)
    2.61
    (0.853)
    1.88
    (0.835)
    1.50
    (0.868)
    PR interval, 78 weeks (n=221, 220, 222)
    2.62
    (1.034)
    3.27
    (1.026)
    1.21
    (1.043)
    26. Secondary Outcome
    Title Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum)
    Description 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.
    Time Frame Baseline, 26, 52, 78, and 83 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one dose of LY2189265 with evaluable LY2189265 ADA data.
    Arm/Group Title LY2189265 1.5 mg and 0.75 mg
    Arm/Group Description LY2189265 (Dulaglutide): 1.5 milligrams (mg) or 0.75 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
    Measure Participants 539
    26 weeks
    11
    4%
    52 weeks
    3
    1.1%
    78 weeks
    1
    0.4%
    83 weeks
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Arm/Group Description 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 (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: 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
    All Cause Mortality
    LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 32/273 (11.7%) 28/272 (10.3%) 33/262 (12.6%)
    Blood and lymphatic system disorders
    Anaemia 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Cardiac disorders
    Acute coronary syndrome 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Acute myocardial infarction 0/273 (0%) 0 2/272 (0.7%) 2 0/262 (0%) 0
    Angina pectoris 1/273 (0.4%) 1 1/272 (0.4%) 1 1/262 (0.4%) 1
    Angina unstable 0/273 (0%) 0 2/272 (0.7%) 2 0/262 (0%) 0
    Atrioventricular block second degree 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Cardiac failure 1/273 (0.4%) 1 2/272 (0.7%) 2 1/262 (0.4%) 1
    Coronary artery disease 1/273 (0.4%) 1 0/272 (0%) 0 2/262 (0.8%) 2
    Myocardial infarction 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Ventricular tachycardia 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Eye disorders
    Cataract 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Macular fibrosis 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Faecaloma 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Gastrointestinal haemorrhage 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Inguinal hernia 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Pancreatitis 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Upper gastrointestinal haemorrhage 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    General disorders
    Chest pain 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Fatigue 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Sudden death 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Hepatobiliary disorders
    Cholelithiasis 1/273 (0.4%) 1 1/272 (0.4%) 1 2/262 (0.8%) 2
    Nodular regenerative hyperplasia 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Infections and infestations
    Anal abscess 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Bronchopneumonia 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Diabetic foot infection 1/273 (0.4%) 1 0/272 (0%) 0 1/262 (0.4%) 1
    Gangrene 0/273 (0%) 0 1/272 (0.4%) 1 1/262 (0.4%) 1
    Gastroenteritis 2/273 (0.7%) 2 0/272 (0%) 0 0/262 (0%) 0
    Hepatitis e 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Localised infection 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Lower respiratory tract infection 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Mastoiditis 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Osteomyelitis 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Pneumonia 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Injury, poisoning and procedural complications
    Fall 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Lower limb fracture 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Maternal exposure during pregnancy 0/129 (0%) 0 0/136 (0%) 0 1/128 (0.8%) 1
    Meniscus lesion 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Overdose 3/273 (1.1%) 3 0/272 (0%) 0 0/262 (0%) 0
    Post procedural haematoma 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 2
    Skeletal injury 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Spinal fracture 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Tendon rupture 1/273 (0.4%) 1 0/272 (0%) 0 1/262 (0.4%) 1
    Investigations
    Blood pressure increased 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Pancreatic enzymes increased 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Metabolism and nutrition disorders
    Dehydration 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Hyperglycaemia 3/273 (1.1%) 3 0/272 (0%) 0 0/262 (0%) 0
    Hypoglycaemia 2/273 (0.7%) 2 0/272 (0%) 0 2/262 (0.8%) 2
    Metabolic syndrome 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Osteoarthritis 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Bladder papilloma 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Bowen's disease 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Breast cancer 0/273 (0%) 0 0/272 (0%) 0 2/262 (0.8%) 2
    Breast cancer metastatic 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Multiple myeloma 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Ovarian adenoma 0/129 (0%) 0 1/136 (0.7%) 1 0/128 (0%) 0
    Prostate cancer stage 0 1/144 (0.7%) 1 0/136 (0%) 0 0/134 (0%) 0
    Testicular seminoma (pure) 0/144 (0%) 0 1/136 (0.7%) 1 0/134 (0%) 0
    Thyroid cancer 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Transitional cell carcinoma 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Uterine leiomyoma 0/129 (0%) 0 0/136 (0%) 0 1/128 (0.8%) 1
    Nervous system disorders
    Carotid artery stenosis 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Cerebral ischaemia 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Haemorrhagic stroke 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Ischaemic stroke 1/273 (0.4%) 2 0/272 (0%) 0 1/262 (0.4%) 1
    Sciatica 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Spinal cord compression 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Spinal cord ischaemia 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Syncope 1/273 (0.4%) 1 0/272 (0%) 0 1/262 (0.4%) 1
    Transient ischaemic attack 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Renal and urinary disorders
    Calculus ureteric 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Hydronephrosis 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Nephrolithiasis 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Renal failure chronic 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Ureteric stenosis 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Dyspnoea 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Respiratory failure 0/273 (0%) 0 0/272 (0%) 0 1/262 (0.4%) 1
    Sleep apnoea syndrome 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Skin and subcutaneous tissue disorders
    Photosensitivity reaction 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Surgical and medical procedures
    Cholecystectomy 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Coronary arterial stent insertion 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Knee arthroplasty 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Meniscus removal 1/273 (0.4%) 1 0/272 (0%) 0 0/262 (0%) 0
    Vascular disorders
    Femoral arterial stenosis 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Thrombophlebitis 0/273 (0%) 0 1/272 (0.4%) 1 0/262 (0%) 0
    Other (Not Including Serious) Adverse Events
    LY2189265 1.5 mg LY2189265 0.75 mg Insulin Glargine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 199/273 (72.9%) 190/272 (69.9%) 187/262 (71.4%)
    Gastrointestinal disorders
    Abdominal pain 12/273 (4.4%) 14 3/272 (1.1%) 3 5/262 (1.9%) 5
    Abdominal pain upper 14/273 (5.1%) 17 9/272 (3.3%) 11 2/262 (0.8%) 2
    Constipation 12/273 (4.4%) 12 3/272 (1.1%) 3 3/262 (1.1%) 3
    Diarrhoea 29/273 (10.6%) 44 26/272 (9.6%) 36 15/262 (5.7%) 20
    Dyspepsia 19/273 (7%) 20 9/272 (3.3%) 10 6/262 (2.3%) 22
    Nausea 42/273 (15.4%) 56 22/272 (8.1%) 33 4/262 (1.5%) 4
    Vomiting 18/273 (6.6%) 23 10/272 (3.7%) 19 3/262 (1.1%) 3
    Infections and infestations
    Bronchitis 9/273 (3.3%) 10 7/272 (2.6%) 8 14/262 (5.3%) 19
    Influenza 12/273 (4.4%) 13 13/272 (4.8%) 16 14/262 (5.3%) 17
    Nasopharyngitis 16/273 (5.9%) 21 12/272 (4.4%) 16 24/262 (9.2%) 27
    Upper respiratory tract infection 15/273 (5.5%) 21 11/272 (4%) 18 17/262 (6.5%) 22
    Urinary tract infection 12/273 (4.4%) 19 17/272 (6.3%) 24 15/262 (5.7%) 18
    Viral infection 4/273 (1.5%) 4 4/272 (1.5%) 4 8/262 (3.1%) 11
    Investigations
    Pancreatic enzymes increased 13/273 (4.8%) 28 9/272 (3.3%) 11 4/262 (1.5%) 7
    Metabolism and nutrition disorders
    Decreased appetite 10/273 (3.7%) 10 12/272 (4.4%) 14 1/262 (0.4%) 1
    Dyslipidaemia 9/273 (3.3%) 9 8/272 (2.9%) 8 4/262 (1.5%) 4
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/273 (1.1%) 3 8/272 (2.9%) 9 12/262 (4.6%) 14
    Back pain 5/273 (1.8%) 5 11/272 (4%) 11 8/262 (3.1%) 10
    Pain in extremity 12/273 (4.4%) 12 10/272 (3.7%) 11 3/262 (1.1%) 3
    Nervous system disorders
    Dizziness 9/273 (3.3%) 9 2/272 (0.7%) 2 5/262 (1.9%) 5
    Headache 22/273 (8.1%) 38 9/272 (3.3%) 9 13/262 (5%) 20
    Respiratory, thoracic and mediastinal disorders
    Cough 9/273 (3.3%) 11 8/272 (2.9%) 8 6/262 (2.3%) 7
    Vascular disorders
    Hypertension 12/273 (4.4%) 12 13/272 (4.8%) 13 11/262 (4.2%) 11

    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.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01075282
    Other Study ID Numbers:
    • 11374
    • H9X-MC-GBDB
    First Posted:
    Feb 25, 2010
    Last Update Posted:
    Jan 16, 2015
    Last Verified:
    Jan 1, 2015