Laiba NASIR, Laiba JALAL, Ayesha SIDDIQA, Aiman NASIR, Maryam FAROOQUI, Abdul Hannan SIDDIQUI
European Journal of Therapeutics - 2026;32(1):39-50
Objective: While several meta-analyses have evaluated the cardiovascular (CV) and renal benefits of GLP-1 receptor agonists, including semaglutide, none have specifically investigated its impact on stroke risk reduction. This meta-analysis aims to evaluate the overall effect of semaglutide on reducing stroke risk among populations at high CV-risk. Methods: A comprehensive search was undertaken across PubMed, Scopus, and Cochrane databases up to May 2024. Four eligible studies included randomized controlled trials (RCTs) that compared semaglutide with placebo for cardiovascular outcomes in both diabetic and non-diabetic populations. Primary cerebrovascular endpoints included stroke and its subtypes. Secondary cardiovascular endpoints were all-cause mortality, major adverse cardiovascular events (MACE), and CV-mortality. Statistical analysis was conducted using Review Manager 5.4 and the risk ratios (RR) with 95% confidence interval (CI) were computed employing a random-effects model. Results: Semaglutide demonstrated a modest reduction in stroke risk (RR 0.84, 95% CI 0.70-1.00, P=0.050, I²=21%), approaching statistical significance. It also demonstrated significant benefits in reducing all-cause mortality (RR 0.81, 95% CI 0.70-0.94, P=0.006, I2=42%), MACE (RR 0.81, 95% CI 0.74-0.88, P<0.001, I2=0%), and cardiovascular mortality (RR 0.79, 95% CI 0.67-0.93, P=0.006, I2=28%). Conclusion: The secondary outcomes were significantly reduced, stroke risk reduction was marginal, highlighting semaglutide's promising vascular benefits. The inclusion of only four RCTs and moderate heterogeneity among the trials may limit the generalizability of these findings.
