Abstract Body (Do not enter title and authors here):

Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk. However, its effect in established high cardiovascular disease patients remain underexplored.

Objective
This study aimed to evaluate the association between GLP-1 RA on MACE in patients with established cardiovascular disease.
Methods
We performed a systematic literature search on PubMed, Scopus, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until June 4th, 2025. Studies were eligible for inclusion if they were having two arms, in one with GLP-1 RA and another with placebo. Only cardiovascular outcomes reporting phase III trials were included in the analysis. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant.

Results
Nine RCTs involving 81,266 patients (36,463 receiving GLP-1 RA and 41,288 receiving placebo) were included in the analysis. The mean age of patients was 65 years. Compared with placebo, GLP-1 RA significantly reduced the risk of MACE in established cardiovascular disease patients when compared with placebo (OR, 0.84 (95%CI: 0.80-0.89), P<0.001).

Conclusion: GLP-1 RA significantly reduces cardiovascular events in patients with established CVD, with consistent effects across trials and no evidence of heterogeneity or publication bias. These findings support the use of GLP-1 RA as a cardioprotective therapy in this population.