Aminorroaya Arya, Oikonomou Evangelos K, Biswas Dhruva, Jastreboff Ania M, Khera Rohan
Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA; Cardiovascular Data Science (CarDS) Lab, Yale School of Medicine, New Haven, Connecticut, USA.
Section of Endocrinology and Metabolism, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA; Section of Pediatric Endocrinology, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA; Yale Obesity Research Center (Y-Weight) Yale School of Medicine, New Haven, Connecticut, USA.
J Am Coll Cardiol. 2025 May 20;85(19):1858-1872. doi: 10.1016/j.jacc.2025.03.516. Epub 2025 Mar 30.
BACKGROUND: Tirzepatide-a dual GIP/GLP-1 receptor agonist-exerts pleiotropic effects on cardiometabolic health. OBJECTIVES: The authors sought to investigate the efficacy of tirzepatide in improving different cardiometabolic risk factors across individuals and subpopulations. METHODS: Using an independent, global data-sharing and analytics platform, we performed an individual participant data meta-analysis by pooling data from 7 Phase 3 randomized clinical trials that compared tirzepatide with placebo or standard antihyperglycemic agents in individuals with type 2 diabetes. The study outcomes were the presence of a range of cardiometabolic abnormalities, representing components of metabolic syndrome (MetS) (elevated waist circumference, triglycerides, blood pressure, and fasting blood glucose, and decreased high-density lipoprotein cholesterol), as well as elevated body mass index and MetS (≥3 cardiometabolic abnormalities). Outcomes were modeled using mixed-effects models, with inverse probability weighting to account for study design differences. RESULTS: We included 7,805 participants with a weighted median age of 59 years (Q1-Q3: 51-66 years) and 43.2% women. Over a weighted median treatment duration of 41.0 weeks, tirzepatide reduced the odds of all cardiometabolic abnormalities, ranging from 34% reduction for the odds of decreased high-density lipoprotein cholesterol (OR: 0.66 [95% CI: 0.52-0.84]) to 96% reduction in the odds of elevated body mass index (OR: 0.04 [95% CI:0.02-0.08]), and 72% reduction for the odds of MetS (OR: 0.28 [95% CI: 0.24-0.33]). Tirzepatide's superior efficacy in resolving MetS was consistent across demographic and clinical subpopulations, with higher efficacy in age <65 years vs ≥65 years, and in individuals without vs with baseline use of sodium-glucose cotransporter 2 inhibitors (P for interaction = 0.008 and 0.009, respectively). CONCLUSIONS: This pooled analysis suggests that tirzepatide may improve cardiometabolic abnormalities and resolve MetS in individuals with type 2 diabetes.
背景：替尔泊肽——一种双重GIP/GLP-1受体激动剂——对心脏代谢健康具有多效性作用。 目的：作者旨在研究替尔泊肽在改善个体和亚组人群中不同心脏代谢危险因素方面的疗效。 方法：我们使用一个独立的全球数据共享和分析平台，通过汇总7项3期随机临床试验的数据进行了个体参与者数据荟萃分析，这些试验在2型糖尿病患者中将替尔泊肽与安慰剂或标准降糖药物进行了比较。研究结果是一系列心脏代谢异常的存在，这些异常代表代谢综合征（MetS）的组成部分（腰围、甘油三酯、血压和空腹血糖升高，以及高密度脂蛋白胆固醇降低），以及体重指数升高和MetS（≥3种心脏代谢异常）。使用混合效应模型对结果进行建模，并采用逆概率加权来考虑研究设计差异。 结果：我们纳入了7805名参与者，加权中位数年龄为59岁（四分位间距：51 - 66岁），女性占43.2%。在加权中位数治疗持续时间41.0周内，替尔泊肽降低了所有心脏代谢异常的几率，从高密度脂蛋白胆固醇降低几率的34%（比值比：0.66 [95%置信区间：0.52 - 0.84]）到体重指数升高几率的96%（比值比：0.04 [95%置信区间：0.02 - 0.08]），以及MetS几率的72%（比值比：0.28 [95%置信区间：0.24 - 0.33]）。替尔泊肽在解决MetS方面的卓越疗效在不同人口统计学和临床亚组中是一致的，在年龄<65岁与≥65岁的人群中，以及在未使用与基线使用钠-葡萄糖协同转运蛋白2抑制剂的个体中疗效更高（交互作用P值分别为0.008和0.009）。 结论：这项汇总分析表明，替尔泊肽可能改善2型糖尿病患者的心脏代谢异常并解决MetS。
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