A Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT03730662
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of the trial is to assess the efficacy and safety of tirzepatide taken once a week to insulin glargine taken once daily in participants with type 2 diabetes and increased cardiovascular risk. The study will last about 108 weeks and may include up to 30 visits.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2002
Participants must:
- Have been diagnosed with type 2 diabetes mellitus (T2DM)
- Have HbA1c between ≥7.5% and ≤10.5%
- Be on stable treatment with unchanged dose of at least 1 and no more than 3 types of oral antihyperglycemic drugs, which may only include metformin, SGLT-2 inhibitors, and/or sulfonylureas for at least 3 months before screening
- Have increased risk for cardiovascular (CV) events
- Be of stable weight (± 5%)
- Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening
Exclusion Criteria
Participants must not:
- Have type 1 diabetes mellitus
- Have had chronic or acute pancreatitis any time prior to study entry
- Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring immediate or urgent treatment
- Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss
- Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level >3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if there ALT level is ≤3.0 the ULN for the reference range
- Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months
- Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2
- Have been taking any other diabetes medicines other than metformin, SGLT-2 inhibitors, and/or sulfonylureas during the last 3 months
- Have been taking weight loss drugs, including over-the-counter medications during the last 3 months
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 10 mg Tirzepatide Tirzepatide 10 mg tirzepatide administered SC once a week. 5 mg Tirzepatide Tirzepatide 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. 15 mg Tirzepatide Tirzepatide 15 mg tirzepatide administered SC once a week. Insulin Glargine Insulin Glargine Insulin glargine administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin glargine was 10 IU/day at bedtime, titrated to a FBG \<100 mg/dL, following a treat-to-target (TTT) algorithm.
- Primary Outcome Measures
Name Time Method Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) Baseline, Week 52 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model for post-baseline measures: Variable = Baseline + Pooled Country + Baseline sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
- Secondary Outcome Measures
Name Time Method Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia Baseline through Week 52 The hypoglycemia events were defined by participant reported events with blood glucose \<54mg/dL (\<3.0 mmol/L) or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. Post-baseline comparisons between treatment and control group was evaluated using negative binomial model with variables : Number of episodes = Baseline HbA1c Group (\<=8.5%, \>8.5%) + Pooled Country + Baseline SGLT-2i use Flag (Yes, No) + Treatment, with log (exposure in days/365.25) as an offset variable
Change From Baseline in Body Weight Baseline, Week 52 LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline SGLT-2i use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Change From Baseline in Fasting Serum Glucose Baseline, Week 52 LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline SGLT-2i use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve From Zero to Tau (AUC 0-Tau) of Tirzepatide 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours post dose of Week 7, 15, 23, 35 Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve From Zero to Tau (AUC 0-Tau) of Tirzepatide
Change From Baseline in HbA1c (5 mg) Baseline, Week 52 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Pooled Country + Baseline SGLT-2i use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Baseline, Week 52 The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. LS mean was determined by mixed-model repeated measures (MMRM) model with variables Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline SGLT-2i use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants With HbA1c of <7.0% Week 52 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.
Trial Locations
- Locations (208)
Advanced Research Center
🇺🇸Anaheim, California, United States
Valley Clinical Trials, Inc.
🇺🇸Northridge, California, United States
Marin Endocrine Associates
🇺🇸Greenbrae, California, United States
National Research Institute
🇺🇸Los Angeles, California, United States
Scripps Whittier Diabetes Institute
🇺🇸La Jolla, California, United States
First Valley Medical Group
🇺🇸Lancaster, California, United States
Catalina Research Institute, LLC
🇺🇸Montclair, California, United States
Monterey Endocrine & Diabetes Institute, Inc.
🇺🇸Monterey, California, United States
Desert Medical Group Inc
🇺🇸Palm Springs, California, United States
Havana Research Institute
🇺🇸Pasadena, California, United States
Scroll for more (198 remaining)Advanced Research Center🇺🇸Anaheim, California, United States