Back to resultsA Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus (T2DM)
Primary Purpose
Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Tirzepatide
Semaglutide
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Diabetes Mellitus, Type 2
Eligibility Criteria
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
Sites / Locations
- Profil Institut für Stoffwechselforschung
- Profil Mainz GmbH & Co. KG
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
Tirzepatide 15 mg
Semaglutide 1 mg
Placebo
Arm Description
Participants received 15 milligram (mg) tirzepatide administered subcutaneously (SC) once weekly for 28 weeks.
Participants received 1 mg Semaglutide administered SC once weekly for 28 weeks.
Participants received Placebo administered SC once weekly for 28 weeks.
Outcomes
Primary Outcome Measures
Change From Baseline in Total Clamp Disposition Index (cDI)
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
Change From Baseline in Fasting Glucose
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 Postmeal Glucose
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 Hemoglobin A1c (HbA1c)
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 Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min)
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 Hyperinsulinemic Euglycemic Clamp M-value
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 Glucagon Concentration at Fasting
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
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).
Change From Baseline in Food Intake During Ad Libitum Meal
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03951753
Brief Title
A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus (T2DM)
Official Title
The Effect of Tirzepatide on α and β Cell Function and Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
June 28, 2019 (Actual)
Primary Completion Date
April 8, 2021 (Actual)
Study Completion Date
April 8, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
117 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tirzepatide 15 mg
Arm Type
Experimental
Arm Description
Participants received 15 milligram (mg) tirzepatide administered subcutaneously (SC) once weekly for 28 weeks.
Arm Title
Semaglutide 1 mg
Arm Type
Active Comparator
Arm Description
Participants received 1 mg Semaglutide administered SC once weekly for 28 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received Placebo administered SC once weekly for 28 weeks.
Intervention Type
Drug
Intervention Name(s)
Tirzepatide
Other Intervention Name(s)
LY3298176
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Semaglutide
Intervention Description
Administered SC
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered SC
Primary Outcome Measure Information:
Title
Change From Baseline in Total Clamp Disposition Index (cDI)
Description
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).
Time Frame
Baseline, Week 28
Secondary Outcome Measure Information:
Title
Change From Baseline in Fasting Glucose
Description
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).
Time Frame
Baseline, Week 28
Title
Change From Baseline in Postmeal Glucose
Description
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).
Time Frame
Baseline, Week 28
Title
Change From Baseline in Hemoglobin A1c (HbA1c)
Description
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).
Time Frame
Baseline, Week 28
Title
Change From Baseline in Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min)
Description
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).
Time Frame
Baseline and Week 28
Title
Change From Baseline in Hyperinsulinemic Euglycemic Clamp M-value
Description
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).
Time Frame
Baseline, Week 28
Title
Change From Baseline in Glucagon Concentration at Fasting
Description
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).
Time Frame
Baseline and Week 28
Title
Change From Baseline in Glucagon Concentration at Postmeal
Description
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).
Time Frame
Baseline and Week 28
Title
Change From Baseline in Food Intake During Ad Libitum Meal
Description
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).
Time Frame
Baseline, Week 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Profil Institut für Stoffwechselforschung
City
Neuss
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
41460
Country
Germany
Facility Name
Profil Mainz GmbH & Co. KG
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55116
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35468322
Citation
Heise T, Mari A, DeVries JH, Urva S, Li J, Pratt EJ, Coskun T, Thomas MK, Mather KJ, Haupt A, Milicevic Z. Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):418-429. doi: 10.1016/S2213-8587(22)00085-7. Epub 2022 Apr 22.
Results Reference
derived
Learn more about this trial
A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus (T2DM)
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