Efficacy of GLP-1 Receptor Agonist-Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta-Analysis of Randomized Controlled Trials

IF 3 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes Pub Date : 2025-04-10 DOI:10.1111/1753-0407.70082

Yue Yin, Minghan Zhang, Qiuyu Cao, Lin Lin, Jieli Lu, Yufang Bi, Yuhong Chen

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引用次数: 0

Abstract

Background

The cardioprotective effects of glucagon-like peptide-1 receptor agonist (GLP-1RA)-based therapies in nondiabetic individuals with overweight or obesity remain underexplored. This meta-analysis evaluates their impact on cardiovascular events and metabolic parameters in this population.

Methods

A meta-analysis was conducted using PubMed, Embase, Cochrane, and Web of Science databases from inception to June 18, 2024. Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity. These studies compared GLP-1RA-based therapies with placebo and reported cardiovascular events and metabolic parameters.

Results

A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included. Compared to placebo, GLP-1RA-based therapies significantly reduced the risk of total cardiovascular events (relative risk: 0.81, 95% confidence interval [CI]: [0.76, 0.87]), major adverse cardiovascular events (0.80, [0.72, 0.89]), myocardial infarction (0.72, [0.61, 0.85]), and all-cause mortality (0.81, [0.71, 0.93]). No significant differences were observed in cardiovascular death or stroke. Additionally, GLP-1RA-based therapies were associated with significant reductions in some cardiometabolic parameters. Among GLP-1RA-based therapies, orfroglipron demonstrated strong benefits in reducing systolic blood pressure (mean difference: −7.10 mmHg, 95% CI: [−11.00, −2.70]). Tirzepatide induced the greatest reduction in body mass index (−6.50 kg/m², [−7.90, −5.10]) and hemoglobin A1c concentrations (−0.39%, [−0.52, −0.26]). Retatrutide and semaglutide were most effective in improving lipid profiles and reducing C-reactive protein levels (−1.20 mg/dL, [−1.80, −0.63]), respectively.

Conclusions

In nondiabetic individuals with overweight or obesity, GLP-1RA-based therapies significantly reduce cardiovascular events and improve cardiometabolic parameters. These findings underscore the potential for individualized GLP-1RA-based therapies targeting cardiovascular risk factors.

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GLP-1受体激动剂治疗对无糖尿病肥胖患者心血管事件和心脏代谢参数的疗效：一项随机对照试验的meta分析

以胰高血糖素样肽-1受体激动剂（GLP-1RA）为基础的治疗对超重或肥胖的非糖尿病患者的心脏保护作用仍未得到充分研究。本荟萃分析评估了它们对该人群心血管事件和代谢参数的影响。方法采用PubMed、Embase、Cochrane和Web of Science数据库，从研究开始至2024年6月18日进行meta分析。符合条件的研究是随机对照试验（rct），纳入超重或肥胖的非糖尿病成年人。这些研究比较了基于glp - 1ra的治疗与安慰剂，并报告了心血管事件和代谢参数。结果共纳入29项随机对照试验，涉及9种glp - 1ra类药物，37 348名符合条件的受试者。与安慰剂相比，基于glp - 1ra的治疗显著降低了总心血管事件（相对风险：0.81,95%可信区间[CI]:[0.76, 0.87]）、主要不良心血管事件（0.80,[0.72,0.89]）、心肌梗死（0.72,[0.61,0.85]）和全因死亡率（0.81,[0.71,0.93]）的风险。在心血管死亡或中风方面没有观察到显著差异。此外，基于glp - 1ra的治疗与一些心脏代谢参数的显着降低相关。在基于glp - 1ra的治疗中，orfroglipron在降低收缩压方面显示出强大的益处（平均差值：- 7.10 mmHg, 95% CI:[- 11.00, - 2.70]）。替唑肽诱导体重指数（- 6.50 kg/m2,[- 7.90, - 5.10]）和血红蛋白A1c浓度（- 0.39%,[- 0.52,- 0.26]）的最大降低。利特鲁肽和西马鲁肽在改善脂质谱和降低c反应蛋白水平方面最有效（分别为- 1.20 mg/dL,[- 1.80, - 0.63]）。结论：在超重或肥胖的非糖尿病患者中，基于glp - 1ra的治疗可显著减少心血管事件并改善心脏代谢参数。这些发现强调了针对心血管危险因素的基于glp - 1ra的个体化治疗的潜力。

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来源期刊

Journal of Diabetes ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

2.20%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The Editorial team is international with a unique mix of Asian and Western participation. The Editors welcome submissions in form of original research articles, images, novel case reports and correspondence, and will solicit reviews, point-counterpoint, commentaries, editorials, news highlights, and educational content.