Abstract Body (Do not enter title and authors here):
Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk. However, disparities in MACE outcomes based on body mass index (BMI) and estimated glomerular filtration rate (eGFR) in patients with and without T2DM remain underexplored.
Objective
To evaluate the association between GLP-1 RA use and MACE in patients with or without T2DM, stratified by BMI (more then 30 and less or equal to 30 kg/m2), and eGFR ( more then 60 and less or equal to 60 mL/min/1.73 m2).
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 a 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
Eight RCTs involving 77,190 patients (38,571 receiving GLP-1 RA and 38,619 receiving placebo) were included in the analysis. The mean age of patients was 64 years. Compared with placebo, GLP-1 RA significantly reduced the risk of MACE in both BMI >30 group of patients (OR, 0.86 (95%CI: 0.82–0.92), p<0.001), and in BMI ≤ 30 group (OR, 0.85(95%CI: 0.76-0.94), p<0.001). Across eGFR groups, GLP-1 RA significantly reduced the risk of MACE in both groups of patients with eGFR >60 (OR, 0.85(95%CI: 0.79-0.92), p<0.001), and in eGFR ≤ 60 (OR, 0.84(95%CI: 0.74-0.95), p=0.01) when comparing with placebo.
Conclusion
This most comprehensive meta-analysis of Nine RCTs demonstrates consistent cardiovascular benefits observed across BMI and eGFR. It also highlights the broad applicability of GLP-1 RAs in diverse patient populations at high cardiovascular risk.