Risk of major adverse cardiovascular events and all-cause mortality under treatment with GLP-1 RAs or the dual GIP/GLP-1 receptor agonist tirzepatide in overweight or obese adults without diabetes: a systematic review and meta-analysis.

IF 4.7 2区医学 Q1 CLINICAL NEUROLOGY

Therapeutic Advances in Neurological Disorders Pub Date : 2024-09-25 eCollection Date: 2024-01-01 DOI:10.1177/17562864241281903

Maria-Ioanna Stefanou, Lina Palaiodimou, Aikaterini Theodorou, Apostolos Safouris, Urs Fischer, Peter J Kelly, Jesse Dawson, Mira Katan, Aristeidis H Katsanos, Vaia Lambadiari, Sotirios Giannopoulos, Andrei V Alexandrov, Gerasimos Siasos, Georgios Tsivgoulis

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引用次数: 0

Abstract

Background: Among the currently approved antiobesity medications, the glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, and the dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes.

Objectives: The objective of this study was to evaluate the cardio- and neuroprotective potential of these novel agents in the nondiabetic overweight/obese adult population.

Data sources and methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate the risk of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality in overweight or obese adults without diabetes treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Secondary outcomes included the risk of myocardial infarction (MI) and stroke.

Results: Sixteen RCTs (13 and 3 on GLP-1 RAs and tirzepatide, respectively) comprising 28,168 participants were included. GLP-1 or GIP/GLP-1 RAs reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71-0.89; p < 0.01; I ² = 0) and all-cause mortality (OR: 0.80; 95% CI: 0.70-0.92; p < 0.01; I ² = 0), while there was a trend toward lower cardiovascular-mortality (OR: 0.84; 95% CI: 0.71-1.01; p = 0.06; I ² = 0%) compared to placebo. Additionally, GLP-1 or GIP/GLP-1 RAs reduced the odds of MI (OR: 0.72; 95% CI: 0.61-0.86; p < 0.01; I ² = 0%) and nonfatal-MI (OR: 0.72; 95% CI: 0.61-0.85; p < 0.01; I ² = 0%); while no associations between antiobesity treatment and fatal-MI, stroke, nonfatal, or fatal stroke were uncovered.

Conclusion: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and all-cause mortality in overweight or obese adults without diabetes. Additionally, GLP-1 RAs and GIP/GLP-1 RAs attenuate the risk of MI. Since data on stroke are still limited, future RCTs are warranted to evaluate the neuroprotective potential of these novel antiobesity agents.

Trial registration: PROSPERO CRD42024515966.

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无糖尿病的超重或肥胖成人在接受 GLP-1 RA 或 GIP/GLP-1 受体双重激动剂替扎帕肽治疗后发生主要不良心血管事件和全因死亡率的风险：系统综述和荟萃分析。

背景：在目前获批的抗肥胖药物中，胰高血糖素样肽-1受体激动剂（GLP-1 RA）利拉鲁肽和赛马鲁肽以及葡萄糖依赖性促胰岛素多肽（GIP）/GLP-1 RA替塞帕肽被认为可降低无糖尿病的超重或肥胖患者的心血管风险：本研究旨在评估这些新型药物在非糖尿病超重/肥胖成年人群中的心血管和神经保护潜力：对随机对照临床试验（RCT）进行了系统回顾和荟萃分析，以估算接受GLP-1或GIP/GLP-1 RAs（与安慰剂相比）治疗的无糖尿病超重或肥胖成人发生主要不良心血管事件（MACE）、全因和心血管死亡的风险。次要结果包括心肌梗死（MI）和中风的风险：共纳入了 16 项 RCT（其中 13 项和 3 项分别涉及 GLP-1 RA 和替哌肽治疗），共有 28,168 人参与。与安慰剂相比，GLP-1 或 GIP/GLP-1 RAs 可降低 MACE（几率比 (OR)：0.79；95% 置信区间 (CI)：0.71-0.89；p I 2 = 0）和全因死亡率（OR：0.80；95% CI：0.70-0.92；p I 2 = 0），同时有降低心血管死亡率的趋势（OR：0.84；95% CI：0.71-1.01；p = 0.06；I 2 = 0%）。此外，GLP-1或GIP/GLP-1 RA可降低心肌梗死（OR：0.72；95% CI：0.61-0.86；p I 2 = 0%）和非致命性心肌梗死（OR：0.72；95% CI：0.61-0.85；p I 2 = 0%）的几率；而抗肥胖治疗与致命性心肌梗死、中风、非致命性或致命性中风之间没有关联：结论：GLP-1 和 GIP/GLP-1 RAs 可降低无糖尿病的超重或肥胖成年人的心血管风险和全因死亡率。此外，GLP-1 RAs 和 GIP/GLP-1 RAs 还能降低心肌梗死的风险。由于有关中风的数据仍然有限，因此有必要在未来进行研究性试验，以评估这些新型抗肥胖药物的神经保护潜力：试验注册：PREMCO CRD42024515966。

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来源期刊

Therapeutic Advances in Neurological Disorders CLINICAL NEUROLOGY-

CiteScore

8.30

自引率

1.70%

发文量

审稿时长

15 weeks

期刊介绍： Therapeutic Advances in Neurological Disorders is a peer-reviewed, open access journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of neurology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in neurology, providing a forum in print and online for publishing the highest quality articles in this area.