A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Mellitus
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT03131687
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of this study is to evaluate the efficacy of the study drug tirzepatide in participants with type 2 diabetes mellitus.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 318
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 mg Tirzepatide Placebo 1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly. Placebo Placebo Tirzepatide placebo and dulaglutide placebo administered subcutaneously (SC) once weekly. 5 mg Tirzepatide tirzepatide 5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly. 5 mg Tirzepatide Placebo 5 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly. 10 mg Tirzepatide tirzepatide 10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly. 10 mg Tirzepatide Placebo 10 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly. 15 mg Tirzepatide tirzepatide 15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly. 15 mg Tirzepatide Placebo 15 mg tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly. 1.5 mg Dulaglutide Placebo 1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly. 1 mg Tirzepatide tirzepatide 1 milligrams (mg) tirzepatide administered SC once weekly. Dulaglutide placebo administered SC once weekly. 1.5 mg Dulaglutide Dulaglutide 1.5 mg Dulaglutide administered SC once weekly. Tirzepatide placebo administered SC once weekly.
- Primary Outcome Measures
Name Time Method Change From Baseline to Week 26 in Hemoglobin A1c (HbA1c) Bayesian Dose Response 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 Outcome Measures
Name Time Method Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) Bayesian Dose Response Baseline, Week 12 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.Change From Baseline to Week 26 in HbA1c Baseline, Week 26 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 + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment\*Time.
Change From Baseline in Body Weight Baseline, Week 26 Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with independent variables: Baseline + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment\*Time.
Percentage of Participants With 10% or Greater Body Weight Loss From Baseline Week 26 Percentage of participants with 10% or greater body weight loss from baseline LOCF analyses using Logistic regression model with Baseline value + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin + Treatment as factors.
Change From Baseline in Total Cholesterol Baseline, Week 26 LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment\*Time.
Change From Baseline in Triglycerides Baseline, Week 26 LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment\*Time.
Change From Baseline in Waist Circumference Baseline, Week 26 LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment\*Time.
Change From Baseline to Week 12 in HbA1c Baseline, Week 12 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 + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment\*Time.
Percentage of Participants With 5% or Greater Body Weight Loss From Baseline Week 26 Percentage of participants with 5% or greater body weight loss from baseline last observation carried forward (LOCF) analyses using Logistic regression model with Baseline value + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin + Treatment as factors.
Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) Baseline, Week 26 LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag, Treatment, Time, Treatment\*Time.
Percentage of Participants Reaching the HbA1c Target of ≤6.5% Week 26 Percentage of participants with HbA1c ≤6.5% at Week 26 using a logistic regression model for endpoint used last observation carried forward (LOCF) method including baseline value, baseline BMI Group, baseline Metformin and treatment as factors.
Percentage of Participants Reaching the HbA1c Target of <7.0% Week 26 Percentage of participants with HbA1c \<7.0% at Week 26 using a logistic regression model for endpoint used last observation carried forward (LOCF) method including baseline value, baseline BMI Group, baseline Metformin and treatment as factors.
Number of Participants With Anti-Drug Antibodies Baseline through Week 30 Number of Participants With Anti-Drug Antibodies.
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 Pharmacokinetics (PK): Model Predicted Concentration at Steady State (Css) of Tirzepatide
Change From Baseline in Fasting Blood Glucose Baseline, Week 26 Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates: Baseline + Baseline HbA1C Group + Baseline BMI Group + Baseline Metformin Flag + Treatment + Time + Treatment\*Time.
Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) Baseline, Week 26 LS means were calculated using MMRM model with independent variables: Baseline, Baseline HbA1C Group, Baseline BMI Group, Baseline Metformin Flag,Treatment, time, treatment\*time.
Trial Locations
- Locations (41)
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
🇸🇰Trenčín, Slovakia
"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."
🇸🇰Trenčín, Slovakia
National Research Institute
🇺🇸Los Angeles, California, United States
New Horizon Research Center
🇺🇸Miami, Florida, United States
Palm Research Center
🇺🇸Las Vegas, Nevada, United States
Catalina Research Institute
🇺🇸Montclair, California, United States
Cotton O'Neil Diabetes and Endocrine
🇺🇸Topeka, Kansas, United States
Lillestol Research LLC
🇺🇸Fargo, North Dakota, United States
ActivMed Practices & Research
🇺🇸Methuen, Massachusetts, United States
Manati Center for Clinical Research
🇵🇷Manati, Puerto Rico
Premier Research
🇺🇸Trenton, New Jersey, United States
Palm Harbor Medical Associate
🇺🇸Palm Harbor, Florida, United States
PMG Research Of Charleston LLC
🇺🇸Moncks Corner, South Carolina, United States
Chase Medical Research
🇺🇸Waterbury, Connecticut, United States
Solaris Clinical Research
🇺🇸Meridian, Idaho, United States
Chrysalis Clinical Research
🇺🇸Saint George, Utah, United States
Manhattan Medical Research
🇺🇸New York, New York, United States
The Corvallis Clinic P.C.
🇺🇸Corvallis, Oregon, United States
Consano Clinical Research
🇺🇸Shavano Park, Texas, United States
New Phase Research & Development
🇺🇸Knoxville, Tennessee, United States
Clinical Research Puerto Rico. Inc
🇵🇷San Juan, Puerto Rico
GCM Medical Group PSC
🇵🇷San Juan, Puerto Rico
Iderc P.L.C.
🇺🇸West Des Moines, Iowa, United States
Valley Research
🇺🇸Fresno, California, United States
Anaheim Clinical Trails
🇺🇸Anaheim, California, United States
Artemis Institute For Clinical Research
🇺🇸San Marcos, California, United States
Valley Clinical Trails, Inc
🇺🇸Northridge, California, United States
University Clinical Investigators INC
🇺🇸Tustin, California, United States
Clinical Research of South Florida
🇺🇸Coral Gables, Florida, United States
East Coast Institute For Research
🇺🇸Jacksonville, Florida, United States
Suncoast Research Group, LCC
🇺🇸Miami, Florida, United States
Sensible Healthcare
🇺🇸Ocoee, Florida, United States
Clinical Research Professionals
🇺🇸Saint Louis, Missouri, United States
Aventiv Research
🇺🇸Columbus, Ohio, United States
Dallas Diabetes Endocrine Center
🇺🇸Dallas, Texas, United States
PMG Research Of Knoxville
🇺🇸Knoxville, Tennessee, United States
Encompass Clinical Research
🇺🇸Spring Valley, California, United States
Internal Medicine Center LLC
🇺🇸Mobile, Alabama, United States
"For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician."
🇵🇱Gdynia, Poland
Clinica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária LTDA
🇵🇱Łódź, Poland
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.
🇸🇰Púchov, Slovakia