GLP-1 receptor agonists and aneurysm rupture risk in type 2 diabetes: a multicenter retrospective study

Intracranial aneurysms (IAs) occur in up to 3% of the population, with rupture leading to substantial morbidity and mortality. Preclinical evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1RAs) may provide vascular protection. Their role in IA rupture prevention has not been readily assessed in large human cohorts.

We conducted a retrospective cohort study using the TriNetX Research Network to identify adults with type 2 diabetes mellitus (T2DM) and unruptured IAs between 2008 and 2025. Patients were classified as GLP-1RA users or non-users. Propensity score matching (PSM) was applied to balance demographics, comorbidities, laboratory values, and medication use. The primary outcome was nontraumatic subarachnoid hemorrhage (SAH) at 3- and 5-year follow-up.

A total of 24,776 T2DM patients with unruptured IA(s) were identified: 3119 of those with GLP-1RA prescriptions and 8063 without GLP-1RA prescriptions. After 1:1 PSM, 2651 patients remained in each cohort. GLP-1RA prescriptions were associated with significantly lower risk of SAH diagnoses at 3 years (HR 0.62, 95% CI 0.44-0.88) with a decreased effect at 5 years (HR 0.65, 95% CI 0.47-0.92). Follow-up laboratory values showed no significant differences between groups.

GLP-1RA prescriptions in patients with T2DM and unruptured IAs were associated with reduced risk of aneurysmal rupture. These results suggest a possible stabilizing effect of GLP-1RAs on IAs, although future prospective, imaging-based studies will be required to further investigate this association.