ABSTRACT NUMBER: ESOC2026A1557 EFFICACY AND SAFETY OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS ON STROKE RISK AND CEREBROVASCULAR OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A NETWORK META-ANALYSIS

Abstract Background and aims Patients with type 2 diabetes mellitus (T2DM) are at an increased risk of cerebrovascular events. This study aimed to compare the efficacy of various Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) in reducing stroke risk and other cerebrovascular events, and assessing their safety profiles. Methods We conducted a comprehensive search of four databases (PubMed, Scopus, Web of Science, and Cochrane CENTRAL) up to 12 November 2025. Randomized controlled trials (RCTs) assessing the efficacy and safety of GLP-1 RAs compared to placebo in patients with T2DM were included. A frequentist network meta-analysis was performed, and data were pooled using R software to calculate risk ratios (RRs) with corresponding 95% confidence intervals (CIs). Results Ten studies (67769 patients) were included, evaluating seven GLP-1 RAs: dulaglutide, efpeglenatide, exenatide, semaglutide, liraglutide, albiglutide, and lixisenatide. Compared to placebo, dulaglutide significantly reduced the risk of any stroke (RR: 0.77, 95% CI: 0.63; 0.95), whereas semaglutide was associated with a significantly lower risk of cardiovascular mortality (RR: 0.74, 95% CI: 0.58; 0.96) and serious adverse events (RR: 0.91, 95% CI: 0.86; 0.95). No significant differences were observed between the interventions in terms of ischemic stroke, hypoglycemia, all-cause mortality, or treatment discontinuation. Conclusions The use of GLP-1 RAs in patients with T2DM may reduce the risk of stroke and appears to have a favorable safety profile, as evidenced by semaglutide’s association with a significantly lower risk of mortality and serious adverse events. Further RCTs comparing different GLP-1 RAs are needed to strengthen this conclusion. Conflict of interest Tasneem Hetta: nothing to disclose, Abdallah Abbas: nothing to disclose, Haneen Sabet: nothing to disclose, Ahmed Wahdan Kasem: nothing to disclose, Yassmeen Ahmed Rizk: nothing to disclose, Abdallah Khatatbeh: nothing to disclose, Gergis Altalab: nothing to disclose, Kenzy Rabie: nothing to disclose, Mohamad Marey: nothing to disclose, Hager Youssif: nothing to disclose, Fawaz Al-Mufti: nothing to disclose, Mohammad El-Ghanem: nothing to disclose. Figure 1 - belongs to Results