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Completed

NCT Number: NCT04050553

A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus

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.

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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Hypoglycemia Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Universitätsklinikum Graz

Graz, Styria, 8036, Austria

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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])

Treatment and study plan

Tirzepatide

Drug

Administered SC

Other names: LY3298176

Placebo

Drug

Administered SC

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

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

    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.

Secondary outcomes

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

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

    A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used.

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

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

    A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used.

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

    Time frame: 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).

    A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used.

  4. 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)

    Time frame: Week 12.

    Hypoglycemia symptoms score was measured with the Edinburgh Hypoglycemia Symptom Scale (EHSS) which is a 13-item questionnaire for hypoglycemic symptoms: 10 neuroglycopenic symptoms (6 cognitive dysfunctions: inability to concentrate, blurred vision, anxiety, confusion, difficulty speaking, and double vision; 4 neuroglycopenia: drowsiness, tiredness, hunger, and weakness), and 3 autonomic symptoms (sweating, trembling, and warmness) and participants were asked to rate the intensity of their hypoglycemic symptoms on a 7-point Likert scale (1 = No symptom to 7 = Severe). The total score is the sum of scores from the 13 questions and ranged from 13 to 91. This score was scaled back to the range of 1 to 7 by taking average of the sum of scores (i.e., sum of the scores divided by number of questions), where lower score indicates fewer symptoms.

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

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

    A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used.

  6. Mean Change in Heart Rate From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

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

    A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

A Randomized, Placebo-Controlled, Crossover Study to Investigate the Effect of Once-Weekly Tirzepatide on the Counter-Regulatory Response to Hypoglycemia in Patients With Type 2 Diabetes Mellitus

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Aug 8, 2019
Registry last updated
May 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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