Risk of major adverse cardiovascular events and stroke associated with treatment with GLP-1 or the dual GIP/GLP-1 receptor agonist tirzepatide for type 2 diabetes: A systematic review and meta-analysis.

IF 5.8 3区 医学 Q1 CLINICAL NEUROLOGY European Stroke Journal Pub Date : 2024-09-01 Epub Date: 2024-02-23 DOI:10.1177/23969873241234238
Maria-Ioanna Stefanou, Aikaterini Theodorou, Konark Malhotra, Diana Aguiar de Sousa, Mira Katan, Lina Palaiodimou, Aristeidis H Katsanos, Ioanna Koutroulou, Vaia Lambadiari, Robin Lemmens, Sotirios Giannopoulos, Andrei V Alexandrov, Gerasimos Siasos, Georgios Tsivgoulis
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引用次数: 0

Abstract

Introduction: Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM.

Patients and methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo).

Results: Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p < 0.01; I2 = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p < 0.01; I2 = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p < 0.01; I2 = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p < 0.01; I2 = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p < 0.01; I2 = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p = 0.105; I2 = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p < 0.01; I2 = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p = 0.792; I2 = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction.

Discussion and conclusion: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.

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使用 GLP-1 或 GIP/GLP-1 受体双重激动剂替西帕肽治疗 2 型糖尿病时发生主要不良心血管事件和中风的风险:系统回顾和荟萃分析。
导言:越来越多的证据表明,胰高血糖素样肽-1受体激动剂(GLP-1 RA)可降低2型糖尿病(T2DM)患者的心血管风险。替扎帕肽是首款获准用于 T2DM 的葡萄糖依赖性促胰岛素多肽 GIP/GLP-1 RA:对随机对照临床试验(RCTs)进行了系统回顾和荟萃分析,以估计:(i) 主要不良心血管事件(MACE)的发生率;(ii) 使用 GLP-1 或 GIP/GLP-1 RAs(与安慰剂相比)治疗的 T2DM 患者的中风、致命性和非致命性中风的发生率:共纳入 13 项 RCT(其中 9 项和 4 项分别涉及 GLP-1 RA 和替哌肽治疗),包括 65,878 名 T2DM 患者。与安慰剂相比,GLP-1 RAs 或 GIP/GLP-1 RAs 可降低 MACE(OR:0.87;95% CI:0.81-0.94;p I2 = 37%)、全因死亡率(OR:0.88;95% CI:0.82-0.96;p I2 = 21%)和心血管死亡率(OR:0.88;95% CI:0.80-0.96;p I2 = 14%),GLP-1 与 GIP/GLP-1 RAs 之间无差异。此外,GLP-1 RA 可降低中风(OR:0.84;95% CI:0.76-0.93;p I2 = 0%)和非致命性中风(OR:0.85;95% CI:0.76-0.94;p I2 = 0%)的几率,而致命性中风与 GLP-1RA 之间没有关联(OR:0.80;95% CI:0.61-1.05;p = 0.105;I2 = 0%)。在二次分析中,GLP-1 RAs 可预防缺血性中风(OR:0.74;95% CI:0.61-0.91;p I2 = 0%)和 MACE 复发,但不能预防出血性中风(OR:0.92;95% CI:0.51-1.66;p = 0.792;I2 = 0%)。GLP-1RA或GIP/GLP-1 RA与致命性或非致命性心肌梗死之间没有关联:讨论和结论:GLP-1 和 GIP/GLP-1 RAs 可降低 T2DM 患者的心血管风险和死亡率。虽然有确凿证据表明 GLP-1 RAs 能显著降低 T2DM 患者缺血性中风的风险,但仍需进行专门的 RCT 研究,以评估新型 GIP/GLP-1 RAs 在一级和二级中风预防方面的疗效。
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来源期刊
CiteScore
7.50
自引率
6.60%
发文量
102
期刊介绍: Launched in 2016 the European Stroke Journal (ESJ) is the official journal of the European Stroke Organisation (ESO), a professional non-profit organization with over 1,400 individual members, and affiliations to numerous related national and international societies. ESJ covers clinical stroke research from all fields, including clinical trials, epidemiology, primary and secondary prevention, diagnosis, acute and post-acute management, guidelines, translation of experimental findings into clinical practice, rehabilitation, organisation of stroke care, and societal impact. It is open to authors from all relevant medical and health professions. Article types include review articles, original research, protocols, guidelines, editorials and letters to the Editor. Through ESJ, authors and researchers have gained a new platform for the rapid and professional publication of peer reviewed scientific material of the highest standards; publication in ESJ is highly competitive. The journal and its editorial team has developed excellent cooperation with sister organisations such as the World Stroke Organisation and the International Journal of Stroke, and the American Heart Organization/American Stroke Association and the journal Stroke. ESJ is fully peer-reviewed and is a member of the Committee on Publication Ethics (COPE). Issues are published 4 times a year (March, June, September and December) and articles are published OnlineFirst prior to issue publication.
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