A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus (T2DM)

Phase 1

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: Semaglutide; Drug: Placebo; Drug: Tirzepatide

• Registration Number: NCT03951753
• Lead Sponsor: Eli Lilly and Company

Brief Summary

This is a study for participants with type 2 diabetes mellitus. The main purpose of this study is to learn more about how tirzepatide, semaglutide and placebo affect the body's ability to respond to blood sugar levels after a meal. The study will last up to 40 weeks, including a 28-week treatment period.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-05-14
• Study First Submitted QC: 2019-05-14
• Study First Posted: 2019-05-15
• Study Start: 2019-06-28
• Primary Completion: 2021-04-08
• Study Completion: 2021-04-08
• Status Verified: 2022-06
• Results First Submitted: 2022-06-08
• Results First Submitted QC: 2022-06-08
• Last Update Submitted: 2022-06-08
• Results First Posted: 2023-03-20
• Last Update Posted: 2023-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 117

Inclusion Criteria

• Have T2DM for at least 6 months
• Treated with diet and exercise and stable dose(s) of metformin, with or without 1 additional stable dose of oral antihyperglycemia medication other than metformin, 3 months prior to study entry
• Have a hemoglobin A1c (HbA1c) value at screening of ≥7% and ≤ 9.5 % if on metformin only; or ≥6.5% and ≤9.0% if on metformin in combination with oral antihyperglycemia medications other than metformin
• Have a body mass index (BMI) between 25 and 45 kilograms per square meter (kg/m² ) inclusive, at screening; are of stable weight (±5%) >3 months prior to screening

Exclusion Criteria

• Have a history of proliferative retinopathy or maculopathy as determined by the investigator based on a recent (<1.5 years) ophthalmologic examination
• Impaired renal estimated glomerular filtration rate (eGFR) <45 milliliters per minute per 1.73 square meters (mL/min/1.73 m²) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
• Have a history or current cardiovascular, respiratory, hepatic, renal, GI,endocrine, hematological or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs; of constituting a risk when taking the study drug; or of interfering with the interpretation of data

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Semaglutide 1 mg	Semaglutide	Participants received 1 mg Semaglutide administered SC once weekly for 28 weeks.
Placebo	Placebo	Participants received Placebo administered SC once weekly for 28 weeks.
Tirzepatide 15 mg	Tirzepatide	Participants received 15 milligram (mg) tirzepatide administered subcutaneously (SC) once weekly for 28 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Total Clamp Disposition Index (cDI)	Baseline, Week 28	cDI is defined as the product of the M-value derived from the hyperinsulinemic euglycemic clamp over the last 30 minutes and total insulin secretion (ISR AUC0-120min) derived from the insulin secretion rate based on C-peptide using the using the deconvolution technique divided by the total glucose AUC0-120min from the hyperglycemic clamp portion of the study. Least squares (LS) mean was determined by analysis of covariance (ANCOVA) model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment (Type III sum of squares).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Postmeal Glucose	Baseline, Week 28	Total AUC from time zero to 240 minutes after start of the meal \[AUC0-240min\]) during sMMTT was evaluated. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares) and ANOVA model for baseline measures: Variable = Treatment (Type III sum of squares).
Change From Baseline in Food Intake During Ad Libitum Meal	Baseline, Week 28	Ad libitum meal served buffet-style. Food intake was recorded during a 45 minute period. The sum of the caloric breakdown (carbohydrates, protein, and fats) was calculated from the respective nutritional information of the food items. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares).
Change From Baseline in Fasting Glucose	Baseline, Week 28	Fasting glucose is a test to determine sugar levels in blood sample after an overnight fast. Fasting glucose was measured prior to standardized mixed-meal tolerance tests (sMMTT). LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares).
Change From Baseline in Hemoglobin A1c (HbA1c)	Baseline, Week 28	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 mixed model repeated measures; (MMRM) model for post-baseline measures: Variable = Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares).
Change From Baseline in Hyperinsulinemic Euglycemic Clamp M-value	Baseline, Week 28	Hyperinsulinemic euglycemic clamp M-value is calculated from glucose infusion rate (GIR) over the last 30 minutes, corresponding to steady-state (+150 to +180 minutes), corrected for urine loss and space. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares).
Change From Baseline in Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min)	Baseline and Week 28	Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min) will be determined from C-peptide concentrations using the deconvolution technique. LS mean was determined by ANCOVA model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment (Type III sum of squares).
Change From Baseline in Glucagon Concentration at Fasting	Baseline and Week 28	Glucagon concentration was measured prior to sMMTT. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares).
Change From Baseline in Glucagon Concentration at Postmeal	Baseline and Week 28	Total AUC from time zero to 240 minutes after start of the meal \[AUC0-240min\]) during sMMTT. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares).

Trial Locations

Locations (2)

Profil Institut für Stoffwechselforschung; 🇩🇪 Neuss, Nordrhein-Westfalen, Germany

Profil Mainz GmbH & Co. KG; 🇩🇪 Mainz, Rheinland-Pfalz, Germany