The Impact of Glucagon-Like Peptide-1 Receptor Agonist on the Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis and Systematic Review

BACKGROUND: Since 2005, the cardioprotective effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have garnered attention. The cardioprotective effect could be an added benefit to the use of GLP-1 RA. This systematic review and meta-analysis aimed at summarizing observational studies that recruited type 2 diabetes individuals with fewer cardiovascular (CV) events before enrolling in the research. METHODS: Systematically, the databases were searched for observational studies reporting compound CV events and deaths in type 2 diabetics without having the risk of cardiovascular diseases (CVDs) compared to other glucose-lowering agents. A meta-analysis was carried out using random effects model to estimate the overall hazard ratio (HR) with a 95% confidence interval (CI). Five studies were found eligible for the systematic review including a total of 64,452 patients receiving either liraglutide (three studies) or exenatide (two studies). RESULTS: The pooled HR for major adverse cardiac event (MACE) and extended MACE was 0.72 (95% CI: 0.65 - 0.93, I(2) = 68%) and 0.93 (95% CI: 0.89 - 0.98, I(2) = 29%), respectively. The pooled HR for hospitalization due to heart failure (HHF) and occurrence of HF was 0.84 (95% CI: 0.77 - 0.91, I(2) = 79%) and 0.83 (95% CI: 0.75 - 0.94, I(2) = 95%), respectively. For stroke, GLP-1 RA was associated with a significant risk reduction of 0.86 (95% CI: 0.75 - 0.98, I(2) = 81%). There was no significant myocardial infarction (MI) risk reduction with GLP-1 RA. As for all-cause mortality, the pooled HR for the occurrence of all-cause mortality was 0.82 (95% CI: 0.76 - 0.88, I(2) = 0%). The pooled HR for the occurrence of CV death was 0.75 (95% CI: 0.65 - 0.85, I(2) = 38%). GLP-1 RA therapy was associated with a significantly low risk of MACE, extended MACE, all-cause mortality, and CV mortality. Except for MACE, the heterogenicity among the studies was low. CONCLUSION: We conclude that GLP-1 RA is associated with a low risk of CV events composites and mortality. The findings support the cardioprotective effect of GLP-1 RA.