A Phase 2 Study of Once-Weekly LY3298176 Compared With Placebo and Dulaglutide in Patients With Type 2 Diabetes Mellitus
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 318
- Locations
- 41
- Primary Endpoint
- Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) Bayesian Dose Response
Study Overview
Brief Summary
The purpose of this study is to evaluate the efficacy of the study drug tirzepatide in participants with type 2 diabetes mellitus.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have had type 2 diabetes (T2D) for ≥6 months according to the World Health Organization (WHO) classification.
- •Have HbA1c of 7.0% to 10.5%, inclusive, as assessed by the central laboratory.
- •If on metformin, have been treated with stable doses of metformin for at least 3 months.
- •Have a body mass index (BMI) ≥23 and <50 kilograms per square meter.
Exclusion Criteria
- •Have type 1 diabetes (T1D).
- •Have used any glucose-lowering medication other than metformin within 3 months prior to study entry or during screening/lead-in period or have used any glucagon-like peptide-1 receptor agonists (GLP-1 RAs) at any time in the past.
- •Have had any of the following cardiovascular conditions: acute myocardial infarction (MI), New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident (stroke).
- •Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (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.
- •Have had chronic or acute pancreatitis any time prior to study entry.
- •Have an estimated glomerular filtration rate (eGFR) <45 milliliters/minute/1.73 square meter, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation.
- •Have serum calcitonin ≥20 picograms per milliliter, as determined by the central laboratory at study entry.
- •Have any condition that is a contraindication for use of the GLP-1 RA class (per country-specific labels) at study entry or develop such condition between study entry and randomization.
Arms & Interventions
Placebo
Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly.
Intervention: Placebo (Drug)
1 mg Tirzepatide
1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Intervention: tirzepatide (Drug)
1 mg Tirzepatide
1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Intervention: Placebo (Drug)
5 mg Tirzepatide
5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Intervention: tirzepatide (Drug)
5 mg Tirzepatide
5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Intervention: Placebo (Drug)
10 mg Tirzepatide
10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Intervention: tirzepatide (Drug)
10 mg Tirzepatide
10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Intervention: Placebo (Drug)
15 mg Tirzepatide
15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Intervention: tirzepatide (Drug)
15 mg Tirzepatide
15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly.
Intervention: Placebo (Drug)
1.5 mg Dulaglutide
1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Intervention: Dulaglutide (Drug)
1.5 mg Dulaglutide
1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) Bayesian Dose Response
Time Frame: Baseline, Week 26
HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.This was a Bayesian dose response analysis of HbA1c (%) change from baseline. At baseline: Mean (SD = Standard Deviation) of baseline HbA1c (%). After baseline: Posterior Mean (SD = Posterior Standard Deviation) of HbA1c (%) change from baseline. The Least Squares Mean is Posterior mean.
Secondary Outcomes
- Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) Bayesian Dose Response(Baseline, Week 12)
- Change From Baseline to Week 26 in HbA1c(Baseline, Week 26)
- Change From Baseline in Body Weight(Baseline, Week 26)
- Percentage of Participants With 10% or Greater Body Weight Loss From Baseline(Week 26)
- Change From Baseline in Total Cholesterol(Baseline, Week 26)
- Change From Baseline in Triglycerides(Baseline, Week 26)
- Change From Baseline in Waist Circumference(Baseline, Week 26)
- Change From Baseline to Week 12 in HbA1c(Baseline, Week 12)
- Percentage of Participants With 5% or Greater Body Weight Loss From Baseline(Week 26)
- Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)(Baseline, Week 26)
- Percentage of Participants Reaching the HbA1c Target of ≤6.5%(Week 26)
- Percentage of Participants Reaching the HbA1c Target of <7.0%(Week 26)
- Number of Participants With Anti-Drug Antibodies(Baseline through Week 30)
- Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide(Predose: Week 1,8,12 and 26; Postdose: Week 1,2,4 and 12)
- Change From Baseline in Fasting Blood Glucose(Baseline, Week 26)
- Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)(Baseline, Week 26)