Abstract 4145358: Cardiovascular Outcomes of Glucagon-Like Peptide 1 Receptor Agonists in Patients with or without Diabetes Mellitus, A Meta-Analysis of Randomized Controlled Trials:

Objectives: Glucagon-like peptide 1 receptor agonists (GLP-1RA) have emerged as a class of antihyperglycemic agents that also reduce major adverse cardiovascular events (MACE), as proven by multiple recent randomized controlled trials (RCTs). This meta-analysis aims to present up-to-date evidence on the cardiovascular benefits of GLP-1 RA in patients with and without diabetes. Methods: After a detailed search of the PUBMED, COCHRANE, EMBASE and MEDLINE databases from their inception until May 2024, 12 RCTs comparing GLP-1 RA with placebo were included in this study. The outcomes of interest were MACE (composite of death from cardiovascular causes, myocardial infarction, and stroke), cardiovascular (CV) mortality, all-cause mortality, myocardial infarction (MI), heart failure (HF) hospitalizations, and the incidence of atrial flutter and atrial fibrillation. The results were reported as risk ratios (RR) with 95% confidence intervals (CI) using random effects model. Results: This study included 84,362 participants from 12 RCTs, with a median follow-up period of 12-60 months. Patients receiving GLP-1 RA showed significant reductions in MACE (RR: 0.86, 95% CI: 0.82-0.92, p=0.00001), all-cause mortality (RR: 0.87, 95% CI: 0.83-0.91, p=0.00001), CV mortality (RR: 0.86, 95% CI: 0.80-0.92, p=0.0001), MI (RR: 0.88, 95% CI: 0.80-0.96, p=0.006), and HF-related hospitalizations (RR: 0.85, 95% CI: 0.73-0.98, p=0.02) compared to those receiving placebo. No significant difference was observed in the incidence of atrial fibrillation or flutter between the two treatment groups. Conclusion: The use of GLP-1RA in patients, regardless of their diabetes mellitus status, reduces the incidence of MACE, MI, death, and HF-related hospitalization. These results further support the use of this class of medication in eligible patients.