Comparison of the efficacy and safety of GLP-1 receptor agonists on cardiovascular events and risk factors: A review and network meta-analysis

IF 5.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2025-02-05 DOI:10.1111/dom.16228

Xuedong An PhD, WenJie Sun PhD, Zhige Wen PhD, LiYun Duan PhD, YueHong Zhang PhD, Xiaomin Kang MS, Hangyu Ji PhD, Yuting Sun MS, Linlin Jiang MS, Xuefei Zhao MS, Qing Gao MS, Fengmei Lian PhD

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Abstract

Objective

This study aims to systematically evaluate and perform a systematic review and network meta-analysis comparing the comprehensive cardiovascular protective effects of various glucagon-like peptide-1 receptor agonists (GLP-1RAs), focusing on cardiovascular events and risk factors.

Methods

We searched PubMed, Embase, Cochrane Library and Web of Science from inception to December 15, 2024. Included studies were published randomized controlled trials (RCTs) comparing GLP-1RAs to placebo or other GLP-1RAs. Missing data were standardized, and network meta-analysis was performed using Stata 17.0. Study heterogeneity, publication bias and evidence quality were assessed using the Cochrane Risk of Bias tool and Confidence in Network Meta-Analysis (CINeMA).

Results

As of December 15, 2024, a total of 18 313 articles were retrieved. Based on the inclusion and exclusion criteria, 156 high-quality studies were included, incorporating 144 782 patients and 14 different GLP-1RAs. The network meta-analysis demonstrated low heterogeneity, ensuring the reliability of the results. Comprehensive analysis revealed the following: Efpeglenatide was the most effective in reducing major adverse cardiovascular events. Oral semaglutide shows more significant advantages in reducing all-cause mortality and cardiovascular mortality. Orforglipron excelled in glycaemic control and weight reduction. SC-Semaglutide showed the greatest efficacy in lowering both systolic blood pressure and diastolic blood pressure, Liraglutide showed the greatest efficacy in lowering total cholesterol, Noiiglutide in triglycerides and Taspoglutide in low-density lipoprotein cholesterol, but no GLP-1RAs in high-density lipoprotein cholesterol. GLP-1RAs did not significantly increase the incidence of adverse events, but Orforglipron and Taspoglutide significantly increased the incidence of gastrointestinal adverse events compared with placebo.

Conclusion

This study compared the cardiovascular benefits of different GLP-1RAs, including reductions in cardiovascular events and improvements in multiple cardiovascular risk factors. However, due to limitations in the quantity and quality of the included studies, the conclusions should be interpreted with caution. Future large-scale, high-quality clinical trials are needed to validate these findings and further optimize comprehensive cardiovascular management strategies for patients.

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GLP-1受体激动剂对心血管事件和危险因素的疗效和安全性比较：综述和网络荟萃分析

目的：本研究旨在对各种胰高血糖素样肽-1受体激动剂（glucagon-like peptide-1 receptor agonists, GLP-1RAs）的心血管综合保护作用进行系统评价并进行系统综述和网络meta分析，重点关注心血管事件及其危险因素。方法：检索PubMed、Embase、Cochrane Library和Web of Science，检索时间为建站至2024年12月15日。纳入的研究是发表的随机对照试验（rct），比较GLP-1RAs与安慰剂或其他GLP-1RAs。对缺失数据进行标准化处理，使用Stata 17.0进行网络meta分析。研究异质性、发表偏倚和证据质量采用Cochrane偏倚风险工具和网络meta分析（CINeMA）置信度进行评估。结果：截至2024年12月15日，共检索到18 313篇文献。根据纳入和排除标准，156项高质量研究纳入144782例患者和14种不同的GLP-1RAs。网络荟萃分析显示异质性低，保证了结果的可靠性。综合分析显示：依佩奈肽在减少主要心血管不良事件方面最有效。口服西马鲁肽在降低全因死亡率和心血管死亡率方面表现出更显著的优势。奥利福列酮在控制血糖和减轻体重方面表现优异。SC-Semaglutide在降低收缩压和舒张压方面效果最好，利拉鲁肽在降低总胆固醇、Noiiglutide降低甘油三酯和Taspoglutide降低低密度脂蛋白胆固醇方面效果最好，但在降低高密度脂蛋白胆固醇方面没有GLP-1RAs。GLP-1RAs没有显著增加不良事件的发生率，但与安慰剂相比，奥福格列酮和Taspoglutide显著增加了胃肠道不良事件的发生率。结论：本研究比较了不同GLP-1RAs对心血管的益处，包括减少心血管事件和改善多种心血管危险因素。然而，由于纳入研究的数量和质量的限制，结论应谨慎解释。未来需要大规模、高质量的临床试验来验证这些发现，并进一步优化患者的综合心血管管理策略。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.