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

Ali Rahman; Sura Alqaisi; Sunil E Saith; Rana Alzakhari; Ralph Levy

doi:10.14740/cr1523

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

Cardiol Res. 2023 Aug;14(4):250-260. doi: 10.14740/cr1523. Epub 2023 Jul 12.

Authors

Ali Rahman¹, Sura Alqaisi¹, Sunil E Saith², Rana Alzakhari³, Ralph Levy⁴

Affiliations

¹ Department of Internal Medicine, Memorial Healthcare System, Pembroke Pines, FL 33028, USA.
² Cardiovascular Fellowship Program, Cardiovascular Disease at SUNY Downstate Health Sciences University, Brooklyn, NY, USA.
³ Cardiovascular Fellowship Program, University of Texas Medical Branch Cardiovascular Disease Program, Galveston, TX, USA.
⁴ Department of Memorial Health Cardiology, Cardiovascular Disease at Memorial Healthcare System, Pembroke Pines, FL 33028, USA.

Abstract

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, I² = 68%) and 0.93 (95% CI: 0.89 - 0.98, I² = 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, I² = 79%) and 0.83 (95% CI: 0.75 - 0.94, I² = 95%), respectively. For stroke, GLP-1 RA was associated with a significant risk reduction of 0.86 (95% CI: 0.75 - 0.98, I² = 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, I² = 0%). The pooled HR for the occurrence of CV death was 0.75 (95% CI: 0.65 - 0.85, I² = 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.

Keywords: Cardiovascular events; Diabetes mellitus; Exenatide; GLP-1 receptor agonist; Liraglutide; MACE.