Glucagon-like peptide-1 receptor agonists and the risk of surgical intervention in idiopathic intracranial hypertension: A propensity-matched cohort study.

OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as promising adjuncts for idiopathic intracranial hypertension (IIH) through weight loss and intracranial pressure modulation. Their impact on surgical intervention requirements remains unclear. METHODS: We conducted a retrospective cohort study using the TriNetX Research Network. Adults with IIH (BMI ≥ 25 kg/m2) were included, excluding those with secondary causes of intracranial hypertension or prior surgical intervention. The exposed cohort (n = 7682) included patients prescribed a GLP-1 RA after IIH diagnosis. The control group (n = 54,775) consisted of unexposed patients. Propensity score matching (1:1) was performed for demographics, BMI, comorbidities, and medication use, yielding 6188 patients per cohort. The primary outcome was ventriculoperitoneal shunt (VPS) placement; secondary outcomes included venous sinus stenting (VSS) and optic nerve sheath fenestration (ONSF). Outcomes were assessed at 1- and 2-years using risk ratios and Cox survival analysis. RESULTS: Following propensity score matching, GLP-1 RA exposure was associated with a significantly reduced incidence of VPS placement at both 1 year (RR 0.42; 95% CI 0.23-0.76; p = 0.003) and two years (RR 0.53; 95% CI 0.32-0.86; p = 0.009). VSS incidence was significantly lower in the GLP-1 RA cohort at both 1 year (RR 0.53; CI 0.32-0.88; p = 0.013) and 2 years (RR 0.56; CI 0.35-0.90; p = 0.015). ONSF rates did not differ significantly at either time point. CONCLUSION: In this multi-institutional, propensity-matched cohort, GLP-1 RA use was associated with lower rates of VPS placement and VSS. These findings suggest a potential disease-modifying role for GLP-1 therapy in IIH and support prospective validation.