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

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.