Impact of GLP-1 receptor agonists on stroke, subarachnoid hemorrhage, and intracerebral hemorrhage: a propensity-matched multi-institutional cohort study.

OBJECTIVE: The authors evaluated whether glucagon-like peptide-1 receptor agonists (GLP-1-RAs) improve outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH), spontaneous intracerebral hemorrhage (sICH), and acute ischemic stroke (AIS) and reduce the overall incidence of these events. METHODS: This retrospective study leveraged TriNetX data (2014-2024) to identify patients with aSAH, sICH, or AIS. Individuals receiving exenatide, lixisenatide, semaglutide, dulaglutide, liraglutide, or tirzepatide within 8 weeks of diagnosis were propensity matched to controls. Outcomes (e.g., mortality, rebleeding/recurrence, seizures, hydrocephalus) were assessed at 6 and 12 months; the incidence rates of stroke types were examined at 1 and 2 years. RESULTS: For aSAH patients, GLP-1-RA use at 6 months reduced rebleeding (OR 0.73, p = 0.003) and mortality (OR 0.41, p < 0.001) and at 1 year lowered cognitive deficits (OR 0.63, p = 0.034) and mortality (OR 0.39, p < 0.001). In sICH patients, GLP-1-RAs decreased hydrocephalus (OR 0.37, p = 0.005) and seizures (OR 0.56, p = 0.007) at 6 months, with persistent benefits at 1 year (hydrocephalus, OR 0.38, p = 0.007; seizures, OR 0.63, p = 0.018), alongside lower mortality (OR 0.45-0.40, both p < 0.001) and rebleeding (OR 0.70-0.69, both p < 0.001) rates. In AIS patients, mortality fell at 6 months (OR 0.27, p < 0.001) and 1 year (OR 0.44, p < 0.001), with reduced recurrence (OR 0.60, p < 0.001) and lower hydrocephalus (OR 0.32, p < 0.001) and seizure (OR 0.43, p < 0.001) rates at 6 months. At 1 year, GLP-1-RA users had lower incidence rates of SAH (OR 0.64, p = 0.001), ICH (OR 0.62, p < 0.001), and AIS (OR 0.82, p = 0.003), which were sustained at 2 years (ORs 0.77-0.87, all p < 0.05). Adverse events were similar. CONCLUSIONS: GLP-1-RAs were associated with improved survival and fewer complications across stroke subtypes, plus reduced hemorrhagic and ischemic stroke incidence. Prospective trials are warranted to confirm these observations.