Background: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by elevated intracranial pressure, predominantly affecting young women with obesity. This study evaluates the effectiveness of semaglutide as an adjunctive therapy to standard IIH management using real-world data. Methods: We conducted a retrospective cohort analysis comparing IIH patients receiving semaglutide plus standard therapy versus standard therapy alone. After propensity score matching, we analyzed 635 patients in each cohort. Primary outcomes included papilledema, headache manifestations, visual disturbances, and refractory disease status at 3-months, 6-months, 12-months, and 24-months. Secondary outcomes included BMI changes. Results: Semaglutide demonstrated significant improvements across all outcomes. At three months, the treatment group showed reduced risks of visual disturbances (RR 0.28, 95% CI 0.179-0.440, p=0.0001), papilledema (RR 0.366, 95% CI 0.260-0.515, p=0.0001), and headache (RR 0.578, 95% CI 0.502-0.665, p=0.0001). These benefits persisted through 24 months. Refractory disease risk was reduced by 40% at three months (RR 0.6, 95% CI 0.520-0.692, p=0.0001). The semaglutide group showed progressive BMI reduction, with a baseline-adjusted difference of -1.38 kg/m^2 (95% CI [-1.671, -1.089], p<0.0001) at 24 months. Conclusions: Semaglutide as an adjunctive therapy demonstrates significant and sustained improvements in IIH-related outcomes, including visual disturbances, papilledema, and headache symptoms. These findings suggest semaglutide may be a valuable addition to standard IIH management protocols, particularly for patients with refractory disease.

The project described was supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through CTSA award number: UM1TR004400. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

The project described was supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through CTSA award number: UM1TR004400. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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