A Study of Tirzepatide (LY3298176) Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin
- Registration Number
- NCT04039503
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to placebo in participants with type 2 diabetes that are already on insulin glargine, with or without metformin. Participants will administer tirzepatide or placebo along with their previous glucose lowering medications. The study will last approximately 47 weeks and may include about 23 visits.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 475
- Have been diagnosed with type 2 diabetes mellitus (T2DM) and have been treated with insulin glargine (U100), once daily with or without metformin ≥3 months prior to screening visit.
- Have HbA1c between ≥7.0% and ≤10.5%.
- Have a stable weight (± 5%) for at least 3 months before screening.
- Have a body mass index (BMI) ≥23 kilograms per meter squared (kg/m²) at screening.
- 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 acute treatment.
- Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss.
- Have an estimated glomerular filtration rate <30 mL/minute/1.73 m² [for participants on metformin, estimated glomerular filtration rate <45 mL/min/1.73 m2 (or lower than the country-specific threshold for using the protocol-required dose of metformin per local label)]
- 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 weight loss drugs, including over-the-counter medications during the last 3 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 15 mg Tirzepatide Tirzepatide 15 mg tirzepatide administered SC once a week. Placebo Placebo Placebo administered SC once a week. 5 mg Tirzepatide Tirzepatide 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. 10 mg Tirzepatide Tirzepatide 10 mg tirzepatide administered SC once a week.
- Primary Outcome Measures
Name Time Method Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) Baseline, Week 40 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 with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Baseline, Week 40 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. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment (Type III sum of squares).
Percentage of Participants Achieving an HbA1c Target Value of <5.7% Week 40 Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Change From Baseline in HbA1c (5 mg) Baseline, Week 40 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 with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).
Change From Baseline in Body Weight Baseline, Week 40 Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).
Change From Baseline in Fasting Serum Glucose Baseline, Week 40 Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS Mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Percentage of Participants Who Achieved Weight Loss ≥5% Week 40 Percentage of Participants who Achieved Weight Loss ≥5%.
Percentage Change From Baseline in Daily Mean Insulin Glargine Dose Baseline, Week 40 LS mean was calculated using MMRM model with log (Baseline) + Baseline Metformin Use (Yes, No) + Pooled Country + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia Baseline through Safety Follow-Up (Up to Week 44) 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. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment, with log (exposure in days/365.25) as an offset variable.
Percentage of Participants Achieving an HbA1c Target Value of <7% Week 40 Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A.HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide Week 7, 15, 23 and 39 post dose AUC is a combined measure obtained from Week 7, 15, 23 and 39 and a single averaged measure of AUC was reported.
Trial Locations
- Locations (47)
Valley Endocrine, Fresno
🇺🇸Fresno, California, United States
Sun Coast Clinical Research, Inc
🇺🇸New Port Richey, Florida, United States
Southern New Hampshire Diabetes and Endocrinology
🇺🇸Nashua, New Hampshire, United States
Manhattan Medical Research
🇺🇸New York, New York, United States
Intend Research
🇺🇸Norman, Oklahoma, United States
Milan Kvapil s.r.o.
🇨🇿Praha 4, Czechia
Diacentrum Brandys n.L. s.r.o.
🇨🇿Brandys Nad Labem-Stara Bolesl, Czechia
Diabetologicka ordinace pro dospele
🇨🇿Krnov, Czechia
Diahelp s.r.o., Interni a diabetologicka ambulance
🇨🇿Pardubice, Czechia
Lekarna Dr. Max
🇨🇿Praha 1, Czechia
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