Clinical trial NCT03951753: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-05-15
Enrollment: 117
Sex: ALL
Minimum age (years): 20
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Change From Baseline in Total Clamp Disposition Index (cDI)
timeFrame: Baseline, Week 28
Secondary outcomes:
measure: Change From Baseline in Fasting Glucose
timeFrame: Baseline, Week 28
measure: Change From Baseline in Postmeal Glucose
timeFrame: Baseline, Week 28
measure: Change From Baseline in Hemoglobin A1c (HbA1c)
timeFrame: Baseline, Week 28
measure: Change From Baseline in Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min)
timeFrame: Baseline and Week 28
measure: Change From Baseline in Hyperinsulinemic Euglycemic Clamp M-value
timeFrame: Baseline, Week 28
measure: Change From Baseline in Glucagon Concentration at Fasting
timeFrame: Baseline and Week 28
measure: Change From Baseline in Glucagon Concentration at Postmeal
timeFrame: Baseline and Week 28
measure: Change From Baseline in Food Intake During Ad Libitum Meal
timeFrame: Baseline, Week 28
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Profil Mainz GmbH & Co. KG
state: Rheinland-Pfalz
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
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.