Victorian Heart Institute, Monash University, VIC, Melbourne, Australia.
Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, NY.
Am Heart J. 2024 Jan;267:1-11. doi: 10.1016/j.ahj.2023.09.007. Epub 2023 Sep 25.
Tirzepatide, a once-weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy of tirzepatide have not been definitively assessed in a cardiovascular outcomes trial.
Tirzepatide is being studied in a randomized, double-blind, active-controlled CV outcomes trial. People with type 2 diabetes aged ≥40 years, with established atherosclerotic CV disease, HbA1c ≥7% to ≤10.5%, and body mass index ≥25 kg/m were randomized 1:1 to once weekly subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1.5 mg. The primary outcome is time to first occurrence of any major adverse cardiovascular event (MACE), defined as CV death, myocardial infarction, or stroke. The trial is event-driven and planned to continue until ≥1,615 participants experience an adjudication-confirmed component of MACE. The primary analysis is noninferiority for time to first MACE of tirzepatide vs dulaglutide by demonstrating an upper confidence limit <1.05, which will also confirm superiority vs a putative placebo, and also to determine whether tirzepatide produces a greater CV benefit than dulaglutide (superiority analysis).
Over 2 years, 13,299 people at 640 sites in 30 countries across all world regions were randomized. The mean age of randomized participants at baseline was 64.1 years, diabetes duration 14.7 years, HbA1c 8.4%, and BMI 32.6 kg/m. Overall, 65.0% had coronary disease, of whom 47.3% reported prior myocardial infarction and 57.4% had prior coronary revascularization. 19.1% of participants had a prior stroke and 25.3% had peripheral artery disease. The trial is fully recruited and ongoing.
SURPASS-CVOT will provide definitive evidence as to the CV safety and efficacy of tirzepatide as compared with dulaglutide, a GLP-1 receptor agonist with established CV benefit.
Tirzepatide 是一种每周一次的 GIP/GLP-1 受体激动剂，可降低 2 型糖尿病患者的血糖和体重。Tirzepatide 的心血管（CV）安全性和疗效尚未在心血管结局试验中得到明确评估。
Tirzepatide 正在一项随机、双盲、阳性对照的 CV 结局试验中进行研究。年龄≥40 岁、有明确动脉粥样硬化性 CV 疾病、糖化血红蛋白（HbA1c）≥7%至≤10.5%、体重指数（BMI）≥25 kg/m²的 2 型糖尿病患者按 1:1 随机分为每周一次皮下注射 tirzepatide 最高 15 mg 或 dulaglutide 1.5 mg。主要结局是首次发生任何主要不良心血管事件（MACE）的时间，定义为心血管死亡、心肌梗死或中风。试验为事件驱动，计划继续进行，直至≥1615 名参与者发生经裁决确认的 MACE 组成部分。主要分析是通过证明上置信限<1.05，来证明 tirzepatide 与 dulaglutide 的首次 MACE 时间无差异（非劣效性分析），这也将确认与假定安慰剂相比的优越性，并且还确定 tirzepatide 是否比 dulaglutide 产生更大的 CV 益处（优越性分析）。
在 2 年的时间里，来自全球所有地区 30 个国家的 640 个地点的 13299 人被随机分组。随机参与者的基线平均年龄为 64.1 岁，糖尿病病程 14.7 年，HbA1c 8.4%，BMI 32.6 kg/m²。总体而言，65.0%的患者患有冠心病，其中 47.3%报告有既往心肌梗死，57.4%有既往冠状动脉血运重建。19.1%的参与者有既往中风，25.3%有外周动脉疾病。该试验已全部入组并正在进行中。
SURPASS-CVOT 将提供关于 tirzepatide 与 dulaglutide 相比的 CV 安全性和疗效的明确证据，dulaglutide 是一种具有明确 CV 获益的 GLP-1 受体激动剂。
