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A Study of Tirzepatide (LY3298176) Versus Insulin Lispro (U100) in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin

Phase 3
Completed
Conditions
Type 2 Diabetes
Interventions
Drug: Insulin Lispro (U100)
Registration Number
NCT04537923
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 insulin lispro (U100) three times a day in participants with type 2 diabetes that are already on insulin glargine (U100), with or without metformin.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1428
Inclusion Criteria
  • Have been diagnosed with type 2 diabetes mellitus (T2DM)
  • Have HbA1c between ≥7.5% and ≤11%
  • Have been treated for at least 90 days prior to day of screening with once or twice daily basal insulin with or without stable dose of metformin ≥1500 mg/day and up to maximum approved dose per country specific approved label, sulfonylureas or dipeptidyl peptidase 4 inhibitors
  • Be of stable weight (± 5%) for at least 90 days
  • Have a BMI ≥23 kilograms per meter squared (kg/m²) and ≤45 kg/m² at screening

Exclusion Criteria

  • Have type 1 diabetes mellitus
  • Have had chronic or acute pancreatitis any time prior to study entry
  • Have proliferative diabetic retinopathy or diabetic macular edema or nonproliferative diabetic retinopathy requiring immediate or urgent treatment
  • Have disorders associated with slowed emptying of the stomach, have had any stomach surgeries for the purpose of weight loss, or are chronically taking drugs that directly affect gastrointestinal motility
  • 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
  • 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)]
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Insulin LisproInsulin Lispro (U100)Insulin lispro 100 units per milliliter (U100) administered SC three times a day.
5 mg TirzepatideTirzepatide5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
15 mg TirzepatideTirzepatide15 mg tirzepatide administered SC once a week.
10 mg TirzepatideTirzepatide10 mg tirzepatide administered SC once a week.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 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 with covariates Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) ScoreBaseline, Week 52

The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. PCS score is reported here. PCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by analysis of covariance (ANCOVA) model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares).

Change From Baseline in HbA1cBaseline, 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 with covariates Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Percentage of Participants With HbA1c Target Values <7.0%Week 52

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 Body WeightBaseline, Week 52

LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) ValuesBaseline, Week 52

The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post meal, Midday Premeal, Midday 2-hour Post meal, Evening Premeal, Evening 2-hour Post meal and Bedtime. The daily average was calculated as the average of the 7 blood glucose values collected on a particular day. LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) ScoreBaseline, Week 52

The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. MCS consisted of social functioning, vitality, mental health, and role-emotional scales. MCS score is reported here. MCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by ANCOVA model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares).

Change From Baseline in Fasting Serum GlucoseBaseline, Week 52

LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without HypoglycemiaWeek 52

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Percentage of Participants Who Achieved Weight Loss ≥5%Week 52

Percentage of Participants who Achieved Weight Loss ≥5% is reported here.

Trial Locations

Locations (133)

Syed Research Consultants Llc

🇺🇸

Sheffield, Alabama, United States

Valley Research

🇺🇸

Fresno, California, United States

National Research Institute - Huntington Park

🇺🇸

Panorama City, California, United States

Valley Clinical Trials, Inc.

🇺🇸

Northridge, California, United States

National Research Institute (NRI) - Santa Ana

🇺🇸

Santa Ana, California, United States

Encompass Clinical Research

🇺🇸

Spring Valley, California, United States

University Clinical Investigators, Inc.

🇺🇸

Tustin, California, United States

University of Colorado

🇺🇸

Aurora, Colorado, United States

Excel Medical Clinical Trials

🇺🇸

Boca Raton, Florida, United States

I R & Health Center, Inc.

🇺🇸

Hialeah, Florida, United States

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Syed Research Consultants Llc
🇺🇸Sheffield, Alabama, United States

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