Association Between Glucagon-Like Peptide-1 Receptor Agonists and Major Adverse Cardiovascular Outcomes Based on Race and Sex Among Patients With and Without Diabetes Mellitus: A Meta-Analysis of Nine Randomized Controlled Trials.

Abstract

<h4>Background</h4>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to reduce major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk. However, the efficacy of GLP-1 RAs on the outcomes of MACEs across different racial and sex groups among patients with and without T2DM remains underexplored. Thus, this study aimed to evaluate the association between GLP-1 RAs and MACEs in patients with and without T2DM based on race and sex.<h4>Methods</h4>We conducted a systematic literature search on the PubMed and Scopus databases, as well as ClinicalTrials.gov, for relevant randomized controlled trials (RCTs) from inception to July 5, 2025. Trials were eligible for inclusion if the included adults (≥18 years) had been randomized to a GLP-1 RA versus placebo group, and MACEs were reported as an outcome. Trials combining GLP-1 RAs with other investigational glucose-lowering agents were excluded. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effect model, and a <i>p</i>-value of <0.05 was considered statistically significant.<h4>Results</h4>Nine RCTs involving 81,266 patients were included in the analysis. The mean age of patients was 65 years. Compared with the placebo, GLP-1 RAs significantly reduced the risk of MACEs in males (RR, 0.82; 95% CI: 0.77-0.86; <i>p</i> < 0.001) and females (RR, 0.81; 95% CI: 0.75-0.88; <i>p</i> < 0.001). Meanwhile, across racial groups, GLP-1 RAs significantly reduced the risk of MACEs in Caucasian patients (RR, 0.87; 95% CI: 0.79-0.96; <i>p</i> < 0.001) compared with placebo. However, no significant difference was observed for the risk of MACEs in Black patients (RR, 1.05; 95% CI: 0.72-1.53; <i>p</i> = 0.80) when comparing GLP-1 RAs with placebo.<h4>Conclusion</h4>This meta-analysis demonstrates that GLP-1 RAs significantly reduce the risk of MACEs in both males and females, as well as across various racial groups in patients with or without T2DM. However, the lack of significant benefit in Black patients suggests potential racial disparities in the enrollment and efficacy of GLP-1 RAs for cardiovascular outcomes.