GLP-1 Receptor Agonists in Idiopathic Intracranial Hypertension

Importance: Current treatment options for idiopathic intracranial hypertension (IIH) are limited by efficacy, safety, and sustainability concerns. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), known for promoting weight loss and metabolic regulation, may offer a novel therapeutic approach. Objective: To assess whether GLP-1 RA therapy is associated with improved clinical outcomes in patients with IIH compared with conventional therapies. Design, Setting, and Participants: This retrospective cohort study was conducted using data from the TriNetX US Collaborative Network between 2005 and 2024, with a follow-up duration of 1 year. Electronic health records from 67 health care organizations across the United States were examined. Participants were patients 18 years and older who had IIH. Exposure: Initiation of GLP-1 RA therapy within 6 months of IIH diagnosis. The control group included patients managed with conventional treatments, such as acetazolamide, topiramate, and dietary counseling, without GLP-1 RA exposure. Main Outcomes and Measures: Outcomes included use of non-GLP-1 RA medication, symptoms and signs, procedures, and mortality over 1 year. Outcomes were expressed as risk ratios (RRs) with 95% CI. Results: A total of 44 373 patients with IIH were identified. Before propensity score matching, the cohort included 603 GLP-1 RA users and 43 770 nonusers. The GLP-1 RA group was older (mean SD age, 43.2 13.0 vs 35.5 14.3 years; P < .001) with fewer male patients (n = 60 10.0% vs n = 5879 13.5%; P = .01) and a similar number of female patients (n = 522 86.6% vs n = 36 796 84.3%; P = .13). After matching, 555 GLP-1 RAs users were compared with 555 nonusers. GLP-1 RA use was associated with lower medication use (RR, 0.53; 95% CI, 0.46-0.61; P < .001) and reduced headaches (RR, 0.45; 95% CI, 0.35-0.58; P < .001), visual disturbances or blindness (RR, 0.60; 95% CI, 0.41-0.88; P = .007), and papilledema (RR, 0.19; 95% CI, 0.10-0.34; P < .001). Procedures (RR, 0.44; 95% CI, 0.30-0.63; P < .001) and mortality (RR, 0.36; 95% CI, 0.18-0.73; P = .003) were lower in the GLP-1 RA group, but mean (SD) body mass index (BMI) did not differ at follow-up (40.6 9.2 vs 39.5 8.7; P = .10). Sensitivity analysis stratified by BMI (≥40 vs <40) showed similar associations. Bariatric surgery was associated with greater weight loss, but GLP-1 RA therapy was associated with better outcomes. Conclusions and Relevance: GLP-1 RA therapy in IIH is associated with significant reductions in medication use, symptoms/signs, and procedural interventions, suggesting its potential as a management strategy. Further prospective studies are warranted to confirm these findings.