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

INTRODUCTION

Idiopathic intracranial hypertension (IIH) remains a challenging condition to manage, with limited therapeutic options. This study investigated the potential of metformin as a novel treatment for IIH, exploring its effects on disease outcomes and safety profile.

METHODS

We conducted a retrospective cohort study using the TriNetX database, analyzing data from 2009 to August 2024. Patients diagnosed with IIH were included, with exclusions for other causes of elevated intracranial pressure and pre-existing diabetes. Propensity score matching was employed to balance cohorts according to age, sex, race, ethnicity, Hemoglobin A1C, and baseline body mass index (BMI) at the time of metformin initiation. Outcomes were assessed at various follow-up points up to 24 months.

RESULTS

Our study initially comprised 1,268 patients in the metformin group and 49,262 in the control group, with notable disparities in several parameters. Post-matching, both cohorts were refined to 1,267 patients each after matching with metformin group. Metformin-treated patients showed significantly lower risks of papilledema, headache, and refractory IIH status at all follow-up points (p<0.0001). The metformin group also had reduced rates of therapeutic spinal punctures and acetazolamide continuation. BMI reductions were more pronounced in the metformin group, with significant differences observed from 6 months onward (p<0.0001). Notably, metformin's beneficial effects persisted independently of BMI changes. The safety profile of metformin was favorable, with no significant differences in adverse events compared to the control group which did not receive metformin during the study timeframe.

CONCLUSIONS

Our study provides evidence for metformin's potential as a disease-modifying therapeutic approach in IIH, demonstrating improvements across multiple outcomes. The benefits appear to extend beyond weight loss, suggesting complex mechanisms of action. These findings warrant further investigation through prospective clinical trials to establish metformin's role in IIH management and explore its underlying therapeutic mechanisms.