A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus

NCT04050553 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 17222I8F-MC-GPHG2019-001360-29
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to learn more about how tirzepatide affects the body's response to low blood sugar (hypoglycemia). The study is open to participants with type 2 diabetes. It will last about 42 weeks for each participant.

Conditions

Diabetes Mellitus, Type 2; Hypoglycemia

Outcome Measures

Primary Outcomes (1)

• Change in Mean Glucagon Concentration During Induced Hypoglycemia From Target Plasma Glucose (PG) Concentration of 100 Milligrams Per Deciliter (mg/dL) to a Nadir Target of 45 mg/dL

  A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using restricted maximum likelihood (REML) method was used. PG of plateau 100 mg/dL was considered as baseline timepoint.

  Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

Secondary Outcomes (6)

• Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

  Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

• Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

  Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

• Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)

  Week 12 in each treatment period (treatment period = 12 weeks): 1 minute after reaching the nadir glucose level and when reaching normoglycemia (estimated as 30 mins).

• Hypoglycemia Symptoms Score From Induced Hypoglycemia at Target PG Concentrations of 100 mg/dL, 63 mg/dL, 45 mg/dL and Recovery (PG Concentration 72 mg/dL)

  Week 12.

• Mean Change in Blood Pressure From Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

  Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

Study Arms (2)

Tirzepatide

EXPERIMENTAL

Participants received a starting dose of 2.5 mg tirzepatide once weekly (QW) for 2 weeks, followed by an increase to 5 mg QW for 2 weeks, and 10 mg QW for 4 weeks until the 15-mg dose was reached and maintained for the remainder of the treatment period (4 weeks) administered subcutaneously (SC) in one of two study periods.

Drug: Tirzepatide

Placebo

PLACEBO COMPARATOR

Participants received placebo QW administered SC in one of two study periods.

Drug: Placebo

Interventions

Tirzepatide DRUG

Administered SC

Also known as: LY3298176

Tirzepatide

Placebo DRUG

Administered SC

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have type 2 diabetes mellitus (T2DM) for at least 1 year
• Treated with diet and exercise and stable dose(s) of metformin 3 months prior to study entry with or without 1 additional oral antidiabetic medication (OAM) other than metformin.
• Have a hemoglobin A1c (HbA1c) value at screening of ≥6.5% and ≤9.0 % if on metformin only.
• Have a HbA1c value at screening of ≥6.0% and ≤8.5 %, if on metformin and 1 more allowed OAM.
• Have a body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m²) inclusive, at screening
• Are of stable weight (±5%) \>3 months prior to screening

You may not qualify if:

• Have a history of proliferative retinopathy or maculopathy as determined by the investigator based on a recent (\<6 months) ophthalmologic examination
• Impaired renal estimated glomerular filtration rate (eGFR) \<60 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 of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (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
• Have had acute myocardial infarction, congestive heart failure New York Heart Association Class III or IV, history of or suspected ischemic heart disease, and/or cerebrovascular accident (stroke \[including transient ischemic attack\])

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Universitätsklinikum Graz

Graz, Styria, 8036, Austria

Location

Related Publications (1)

• Pieber TR, Svehlikova E, Urva S, Haupt A, Zhou C, Coskun T, Holler V, Fluhr G, Karanikas CA, Milicevic Z, Pratt EJ. Counterregulatory response to hypoglycemia during a hypoglycemic clamp in people with type 2 diabetes treated with tirzepatide. Front Endocrinol (Lausanne). 2025 Sep 2;16:1627947. doi: 10.3389/fendo.2025.1627947. eCollection 2025.

  PMID: 40964167 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypoglycemia

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: August 8, 2019
• Study Start: February 24, 2020
• Primary Completion: January 25, 2022
• Study Completion: January 25, 2022
• Last Updated: May 20, 2024
• Results First Posted: May 20, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)