Glucagon-Like Peptide-1 Receptor Agonists and Decreased Subarachnoid Hemorrhage Risk in Patients With Intracranial Aneurysm

BACKGROUND: The potential protective effect of GLP‑1RAs against nontraumatic subarachnoid hemorrhage (SAH) in individuals with intracranial aneurysms (IAs) remains unclear. Since GLP-1RAs (glucagon-like peptide-1 receptor agonists) have known anti-inflammatory and antihypertensive properties, we proposed to evaluate whether they reduce the risk of nontraumatic SAH in patients with IA with type 2 diabetes. METHODS: We conducted a retrospective cohort study using the global TriNetX database, which spans over 90 health care organizations across North America, South America, Europe, and Asia, with the majority of data contributed by the United States. Analysis included data from January 2010 to January 2025. Patients with unruptured IAs and type 2 diabetes who received GLP‑1RAs (n=2517) were compared with those who did not (n=23 431). Propensity score matching (1:1) was performed on 95 demographic and clinical variables, including smoking and hypertension. A subgroup and matched analysis excluded patients who had a history of IA treatment. The primary outcomes were nontraumatic SAH and all‑cause mortality over a 5‑year follow‑up period. Hazard ratios (HRs) and 95% CIs were calculated, and a falsification analysis was performed to evaluate whether patients taking GLP-1RAs were receiving more medical care. RESULTS: After matching, each cohort comprised 2275 patients. GLP‑1RA use was associated with a significantly lower rate of nontraumatic SAH (HR, 0.66 [95% CI, 0.50-0.87]) and all‑cause mortality (HR, 0.63 [95% CI, 0.52-0.76]). In the matched subgroup analysis of untreated patients, GLP‑1RA use was similarly associated with reduced risk of nontraumatic SAH (HR, 0.68 [95% CI, 0.47-0.98]) and all‑cause mortality (HR, 0.64 [95% CI, 0.53-0.77]). Falsification analysis confirmed the absence of confounding by indication and health care access bias. CONCLUSIONS: GLP‑1RAs have a potential role in mitigating nontraumatic SAH and improving survival among patients with IA with type 2 diabetes. Prospective trials are warranted to confirm these findings.