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.