Impact of GLP-1 Receptor Agonists on Cardiovascular Risk Reduction in Patients with Type 2 Diabetes

Abstract

Background: Type 2 diabetes mellitus (T2DM) is associated with a significantly increased risk of cardiovascular disease (CVD), the leading cause of morbidity and mortality in this population. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as promising agents not only for glycemic control but also for potential cardiovascular benefits. This systematic review evaluates the impact of GLP-1 RAs on cardiovascular risk reduction in patients with T2DM.

Methods: A comprehensive search was conducted across PubMed, Embase, Scopus, and Web of Science for studies published up to the final search date. Eligible studies included randomized controlled trials (RCTs), prospective cohort studies, and retrospective observational studies that assessed cardiovascular outcomes such as major adverse cardiovascular events (MACE), cardiovascular death, myocardial infarction, or stroke in adults with T2DM. Data were extracted and synthesized narratively due to heterogeneity in study designs and outcomes.

Results: Thirteen studies met the inclusion criteria, predominantly multicenter RCTs involving high-risk T2DM patients

with established CVD or chronic kidney disease (CKD). Key findings demonstrated that GLP-1 RAs, particularly semaglutide, liraglutide, and dulaglutide, significantly reduced the risk of MACE, cardiovascular death, and stroke. For example, the LEADER trial reported a reduction in MACE with liraglutide, while SUSTAIN-6 showed a 26% risk reduction with semaglutide. Improvements in secondary outcomes, such as weight loss and blood pressure reduction, were also noted. However, variability in outcomes was observed, with some agents like lixisenatide showing neutral effects.

Conclusion: GLP-1 RAs offer dual benefits of glycemic control and cardiovascular risk reduction in patients with T2DM, particularly those with high cardiovascular risk. The evidence supports their integration into treatment guidelines for this population. Further research is needed to explore long-term effects, subgroup-specific responses, and comparative efficacy among different GLP-1 RAs. These findings underscore the importance of personalized treatment strategies to optimize cardiovascular outcomes in T2DM..