Early GLP-1 Receptor Agonist Therapy in Acute Ischemic Stroke and High-Risk Transient Ischemic Attack: A Systematic Review and Meta-analysis of Randomized Trials

Background and Objectives: The role of early glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy after acute ischemic stroke or high-risk transient ischemic attack remains uncertain. We performed a systematic review and meta-analysis of randomized evidence evaluating efficacy and safety in this setting. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidance, we included randomized controlled trials evaluating early GLP-1RA therapy in adults with acute ischemic stroke or high-risk transient ischemic attack. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using inverse-variance random-effects models with restricted maximum likelihood estimation. The primary outcome was 90-day functional independence (modified Rankin Scale score: 0–2); mortality and symptomatic intracranial hemorrhage (sICH) were critical safety outcomes. Results: Four randomized trials enrolled 1,514 participants: LAMP, GALLOP-1, GALLOP-2, and TEXAIS. GLP-1RA therapy increased 90-day functional independence (547/745 vs 516/752; RR = 1.06; 95% CI: 1.01–1.11; I² = 5.8%), corresponding to an absolute risk difference of 4.8% and number needed to treat of 21. Mortality did not differ significantly (57/749 vs 52/756; RR = 1.13; 95% CI: 0.80–1.61; I² = 0%). sICH was not significantly different (23/579 vs 20/585; RR = 0.67; 95% CI: 0.13–3.42; I² = 67.0%). Excluding LAMP attenuated the functional effect (RR = 1.07; 95% CI: 0.92–1.24), and excluding GALLOP-2 yielded RR = 1.049 (95% CI: 0.999–1.102). Conclusions: Early GLP-1RA therapy shows a possible functional benefit, but the finding is fragile and safety evidence remains imprecise. Larger dedicated stroke trials are required before routine clinical use.