A Study of the Efficacy and Safety of Dulaglutide (LY2189265) in Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of investigational doses of once weekly dulaglutide when added to metformin in participants with type 2 diabetes with inadequate blood sugar control.

Official Title
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A Randomized, Double-Blind, Parallel Arm Study of the Efficacy and Safety of Investigational Dulaglutide Doses When Added to Metformin in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Dulaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have type 2 diabetes mellitus (T2DM) for at least 6 months Have been treated with stable metformin dose for at least 3 months Have HbA1c ≥7.5% and ≤11.0% at study entry Have body mass index (BMI) ≥25 kilograms per meter squared (kg/m^2) Exclusion Criteria: Have type 1 diabetes mellitus Have used any glucagon-like peptide-1 receptor agonist (GLP-1 RA) or insulin, not including prior short term insulin use (≤14 days) Have been taking any other medicine for diabetes (other than metformin) during the last 3 months Have used in the last 3 months (or plan to use) prescription weight loss medications Have disorders associated with slowed emptying of the stomach contents, or have had any stomach surgeries for the purpose of weight loss Current participation in or intent to begin during the study an organized diet and/or exercise weight reduction program (other than the lifestyle and dietary measures for diabetes) Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine transaminase (ALT) level >2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial Had chronic or acute pancreatitis any time prior to study entry Have had a heart attack or stroke in the past 2 months, or have heart failure that significantly limits their physical activity Estimated glomerular filtration rate (eGFR) <30 milliliters/minute/1.73m^2 (or lower than the country-specific threshold for discontinuing metformin therapy per local label), calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, as determined by the central laboratory at study entry and confirmed at lead-in Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2 Have proliferative retinopathy or maculopathy requiring acute treatment according to the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dulaglutide 1.5 mg<br>Dulaglutide 1.5 mg administered subcutaneously (SC) once a week. | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;|
| Experimental: Dulaglutide 3 mg<br>Dulaglutide 3 mg administered SC once a week. | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;|
| Experimental: Dulaglutide 4.5 mg<br>Dulaglutide 4.5 mg administered SC once a week. | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin A1c (HbA1c) From Baseline | HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables:Baseline + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares). | Baseline, Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight From Baseline | Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with independent variables: Baseline + Baseline HbA1c group + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares). | Baseline, Week 36 | 
| Percentage of Participants Achieving HbA1c Target <7.0% | Percentage of participants achieving HbA1c target <7.0%. | Week 36 | 
| Change in Fasting Serum Glucose (FSG) From Baseline | Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates: Baseline + Baseline HbA1c group + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares). | Baseline, Week 36 | 
| Rate of Documented Symptomatic Hypoglycemic Episodes | Hypoglycemia was defined as blood glucose < 54 mg/dL, excluding post-rescue records. Estimate is based on Group Mean from negative binomial model. The negative binomial model for post-baseline comparisons between treatments and control group: Number of episodes = Pooled Country + HbA1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable. | Week 36 | 
| Pharmacokinetic (PK): Steady-state Maximum Concentration(Cmax,ss) | Pharmacokinetic (PK): Steady-state Maximum Concentration(Cmax,ss). | Week 4, Week 12, Week 36, Week 52 | 
| Pharmacokinetic (PK): Area Under the Curve AUC (0-168)ss at Steady State | Pharmacokinetic (PK): Area Under the Curve AUC (0-168)ss at Steady State. | Week 4, Week 12, Week 36, Week 52 |