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

Abstract

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. 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. 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. 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.