The efficacy and safety of GLP-1 agonists to modify cardiovascular morbidity in patients with obesity without diabetes mellitus: a meta-analysis involving 32,884 patients

Abstract Background While the cardioprotective effects of glucagon-like peptide -1 (GLP-10) agonists are well-documented in diabetic patients, their impact on cardiovascular outcomes in patients with obesity without diabetes mellitus remains debated. Purpose This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of GLP-1 on cardiovascular outcomes in patients with obesity without diabetes mellitus. Methods A systematic review and meta-analysis synthesizing RCTs were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through December 26th, 2023. Dichotomous data were pooled using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Results We included 19 RCTs with a total of 32,884 patients. There was no difference between GLP-1 agonists and placebo regarding cardiovascular mortality (RR: 0.85, 95% CI [0.71- 1.01], P= 0.07). However, GLP-1 agonists significantly decreased the incidence of all-cause mortality (RR 0.83, 95% CI 0.72 to 0.94, p < 0.0001), non-cardiovascular mortality (RR 0.78, 95% CI 0.63 to 0.96, p = 0.02), and myocardial infarction (RR 0.73, 95% CI 0.62 to 0.87, p < 0.0001). Also, GLP-1 agonists significantly increased the incidence of any adverse events (RR 1.11, 95% CI 1.05 to 1.16, p < 0.0001), with no difference regarding the incidence of serious adverse events. Conclusion GLP-1 agonists not only demonstrated substantial benefits in reducing cardiovascular risks, including all-cause mortality and myocardial infarction, but also effectively promoted weight loss and improved lipid profiles and blood pressure control. However, their use is accompanied by a higher incidence of gastrointestinal adverse effects and heterogeneity in outcomes, highlighting the need for individualized treatment approaches.