Cardiovascular Outcomes and Safety of GLP-1 Receptor Agonists in Elderly Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Weifei Gao, Xiaoming Cai, Xiaolu Wang, Peng Li Department of General Practice, Hangzhou Third People’s Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Peng Li, Department of General Practice, Hangzhou Third People’s Hospital, No. 38, Xihu Avenue, Shangcheng District, Hangzhou, Zhejiang, 310000, People’s Republic of China, Email [email protected]: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes. However, evidence specific to elderly patients remains limited. Elderly patients with diabetes are associated with high cardiovascular (CV) risk and increased susceptibility to adverse events. Therefore, this study systematically evaluated the CV outcomes and safety of GLP-1 RAs in elderly patients with T2DM.Methods: PubMed, Embase and Web of Science were searched for randomized controlled trials (RCTs) published up to January 2024 that compared GLP-1 RAs with placebo or other controls in patients aged ≥ 65 years, with cardiovascular outcomes as the primary endpoint. Safety outcomes, including gastrointestinal adverse events and hypoglycemia, were also analyzed. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model.Results: The review was registered with PROSPERO (CRD42024582164). Of 2,425 screened articles, five full-text publications (reporting six independent RCTs) involving 8,889 patients were included. The mean age was 71.8 years. Compared with placebo, GLP-1 RAs significantly reduced MACE by 21% (RR 0.79, 95% CI 0.70– 0.90; p = 0.0003) and non-fatal myocardial infarction by 25% (RR 0.75, 95% CI 0.62– 0.91; p = 0.003). No significant reductions were observed in cardiovascular mortality (RR 0.86, 95% CI 0.69– 1.07; p = 0.17) or non-fatal stroke (RR 0.91, 95% CI 0.70– 1.18; p = 0.49). GLP-1 RAs were associated with increased risks of diarrhea (RR 2.33, 95% CI 1.35– 4.01; p = 0.002) and nausea (RR 2.94, 95% CI 1.66– 5.21; p = 0.0002).Conclusion: These findings suggest that GLP-1 RAs confer significant cardioprotective benefits in elderly patients with T2DM, although gastrointestinal adverse effects warrant careful monitoring.Keywords: GLP-1 receptor agonist, older, semaglutide, liraglutide, albiglutide