Safety and Efficacy of Metformin for Idiopathic Intracranial Hypertension. A U.S-Based Real-World Data Retrospective Multicenter Cohort Study.

Introduction: Managing idiopathic intracranial hypertension (IIH) is challenging due to limited treatment options. This study evaluates metformin as a potential therapy for IIH, examining its impact on disease outcomes and safety. Methods: We performed a retrospective cohort study using the TriNetX database, covering data from 2009 to August 2024. The study included IIH patients, excluding those with other causes of raised intracranial pressure or pre-existing diabetes. Propensity score matching adjusted for age, sex, race, ethnicity, Hemoglobin A1C, and baseline BMI at metformin initiation. We assessed outcomes up to 24 months. Results: Initially, 1,268 patients received metformin and 49,262 served as controls, showing disparities in various parameters. After matching, both groups consisted of 1,267 patients each. Metformin users had significantly lower risks of papilledema, headache, and refractory IIH at all follow-ups (p<0.0001). They also had fewer spinal punctures and reduced acetazolamide use. BMI reductions were more significant in the metformin group from 6 months onward (p<0.0001), with benefits persisting regardless of BMI changes. Metformin's safety profile was comparable to the control group. Conclusions: The study indicates metformin's potential as a disease-modifying treatment in IIH, with improvements across multiple outcomes independent of weight loss. This suggests complex mechanisms at play, supporting further research through prospective clinical trials to confirm metformin's role in IIH management and its mechanisms of action.