肠促胰岛素类似物在非糖尿病肥胖成年人心血管结局及肥胖和糖尿病以外的其他经典心血管危险因素中的作用：一项随机对照试验的荟萃分析
Role of Incretin Mimetics in Cardiovascular Outcomes and Other Classical Cardiovascular Risk Factors beyond Obesity and Diabetes Mellitus in Nondiabetic Adults with Obesity: a Meta-analysis of Randomized Controlled Trials.
作者信息
Kamarullah William, Pranata Raymond, Wiramihardja Siska, Tiksnadi Badai Bhatara
机构信息
Department of Cardiology and Vascular Medicine, Faculty of Medicine, Padjadjaran University, Jl. Pasteur No. 38, Pasteur, Kec. Sukajadi, Kota Bandung, Jawa Barat, Indonesia.
Division of Medical Nutrition, Department of Public Health, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia.
出版信息
Am J Cardiovasc Drugs. 2025 Mar;25(2):203-229. doi: 10.1007/s40256-024-00695-9. Epub 2024 Nov 30.
BACKGROUND
Emerging data on cardiovascular outcomes, specifically major adverse cardiovascular events (MACE), are being reported from various trials involving incretin mimetics, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and glucose-dependent insulinotropic polypeptide (GIP), especially among patients with obesity and diabetes. Our aim was to evaluate this matter, while also involving various traditional cardiovascular risk factors [e.g., several body weight (BW) parameters, blood pressure (BP), lipid profile].
METHODS
A search of PubMed, Europe PMC, ScienceDirect, Cochrane, and ClinicalTrials.gov up to September 2024 was performed to identify GLP-1 RA and GIP trials in MACE risk reduction as a primary endpoint. Our secondary endpoints included a reduction in BW, waist circumference (WC), body mass index (BMI), BP changes, and lipid modifying effects, while also yielding safety concerns surrounding the use of these pharmaceutical agents. Mean differences (MD) and risk ratios (RR) were summarized using random-effects model.
RESULTS
A total of 11 eligible randomized controlled trials (RCTs) comprising 8 GLP-1 RA trials and 3 dual GLP-1 RA/GIP (tirzepatide) trials were included. Compared with control groups, GLP-1 RA significantly reduced the MACE risk by 32% [RR 0.68 (95% CI 0.53-0.87); P = 0.002; I = 73%, P-heterogeneity < 0.001] and 59% for tirzepatide [RR 0.41 (95% CI 0.18-0.92); P = 0.03; I = 0%, P-heterogeneity = 0.96]. Incretin mimetics also substantially reduced BW, BP, and improved lipid panel measures. However, there was an increased risk of adverse events, specifically gastrointestinal disorders within the incretin mimetics subset.
CONCLUSIONS
Incretin mimetics have shown promise in reducing MACE risk while also enhancing cardiovascular risk factors, including blood pressure and lipid profile, in adults with obesity without diabetes.
背景
关于心血管结局，特别是主要不良心血管事件（MACE）的新数据，正从涉及肠促胰岛素类似物的各种试验中被报道出来，如胰高血糖素样肽-1受体激动剂（GLP-1 RA）和葡萄糖依赖性促胰岛素多肽（GIP），尤其是在肥胖和糖尿病患者中。我们的目的是评估这一问题，同时纳入各种传统心血管危险因素[例如，多个体重（BW）参数、血压（BP）、血脂谱]。
方法
检索截至2024年9月的PubMed、欧洲PMC、ScienceDirect、Cochrane和ClinicalTrials.gov，以确定以降低MACE风险作为主要终点的GLP-1 RA和GIP试验。我们的次要终点包括体重减轻、腰围（WC）减小、体重指数（BMI）降低、血压变化以及血脂改善效果，同时还要关注使用这些药物制剂的安全性问题。使用随机效应模型汇总平均差（MD）和风险比（RR）。
结果
总共纳入了11项符合条件的随机对照试验（RCT），其中包括8项GLP-1 RA试验和3项双靶点GLP-1 RA/GIP（替尔泊肽）试验。与对照组相比，GLP-1 RA使MACE风险显著降低32%[RR 0.68（95%CI 0.53 - 0.87）；P = 0.002；I² = 73%，P异质性<0.001]，替尔泊肽则降低59%[RR 0.41（95%CI 0.18 - 0.92）；P = 0.03；I² = 0%，P异质性 = 0.96]。肠促胰岛素类似物还能显著减轻体重、降低血压并改善血脂指标。然而，不良事件风险有所增加，特别是在肠促胰岛素类似物亚组中的胃肠道疾病。
结论
肠促胰岛素类似物在降低无糖尿病肥胖成年人的MACE风险方面显示出前景，同时还能改善包括血压和血脂谱在内的心血管危险因素。
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