Efficacy of glucagon-like peptide-1 receptor agonists for prevention of stroke among patients with and without diabetes: A meta-analysis with the SELECT and FLOW trails

Central Illustration: Efficacy of glucagon-like peptide-1 receptor agonists for prevention of stroke among patients with and without diabetes: a meta-analysis with the SELECT and FLOW trails. • GLP-1 receptor agonists have shown cardioprotective effects in previous meta -analyses among diabetic patients. • This present meta analysis has the novelty of including most recently published randomized trials such as FLOW, and SELECT trials and patients with a wide spectrum of disease evaluating risk of stroke and adverse events related to stroke. • GLP-1 receptor agonists has beneficial effects in reducing the risk of stroke, and nonfatal stroke in patients with and without diabetes. • Adverse events related to stroke were comparable, and risk of cerebrovascular accident was lower among GLP-1 receptor agonists group of patients. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). However, its efficacy on cerebrovascular events is yet to be well established among diabetic and non diabetic patients. We sought to evaluate the efficacy of GLP-1 RAs on stroke risk among its different types in patients with and without Diabetes. We performed a systematic literature search on PubMed, EMBASE, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) from inspection until 15th July 2024, without any language restrictions. Odds ratios (OR) and 95 % confidence intervals (CI) were pooled using a random-effect model, and a p-value of < 0.05 was considered statistically significant. A total of 11 RCTs with 85,373 patients were included (43,339 in GLP-1 RA and 42,034 in the placebo group) in the analysis. The mean age of the patients in GLP-1 RAs and the placebo groups was 63.5 and 63.1 years, respectively. Pooled analysis of primary and secondary endpoints showed that GLP-1 RAs significantly reduced the risk of incidence of stroke by 15 % (OR, 0.85(95 %CI: 0.77–0.93), P < 0.001) and nonfatal stroke by 13 % (OR, 0.87(95 %CI: 0.79–0.95), P < 0.001) compared with placebo. However, the risk of fatal stroke (OR, 0.94(95 %CI: 0.75–1.17), P = 0.56) was comparable between both groups of patients. Similarly, the risk of serious adverse events such as cerebrovascular accident (OR, 0.75(95 %CI: 0.57–1.00), P = 0.05), hemorrhagic stroke (OR, 0.82(95 %CI: 0.42–1.60), P = 0.57, and ischemic stroke (OR, 0.85(95 %CI: 0.64–1.13), P = 0.26) was comparable between GLP-1RAs and placebo. Treatment with GLP-1 receptor agonists has beneficial effects in reducing the risk of stroke, and nonfatal stroke in patients with and without diabetes. However, no such effect was observed for fatal stroke.