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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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])
研究组 & 干预措施
Tirzepatide
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.
干预措施: Tirzepatide (Drug)
Placebo
Participants received placebo QW administered SC in one of two study periods.
干预措施: Placebo (Drug)
结局指标
主要结局
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
时间窗: 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.
次要结局
- 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.)
- Mean Change in Heart Rate 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.)