Risk of Non‐Arteritic Anterior Ischemic Optic Neuropathy in Idiopathic Intracranial Hypertension Patients Treated with <scp>GLP</scp> ‐1 Receptor Agonists

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant weight-reducing effects and may offer benefits in idiopathic intracranial hypertension (IIH); however, recent concerns about the risk of non-arteritic anterior ischemic optic neuropathy (NAION) have emerged. Hence, this study was designed to examine the relationship between GLP-1 RA use and optic outcomes in IIH patients. METHODS: This study used the TriNetX Global Collaborative Network to perform a retrospective propensity score-matched cohort study. It involved GLP-1 RA exposure status to classify adult patients with IIH. Further, it applied propensity score matching (PSM) on demographics, comorbidities, and medications. In this study, the primary outcome was incident NAION; the secondary outcome was optic atrophy. Cox proportional hazards regression, time-stratified analyses, and multiple testing corrections were performed. RESULTS: From 144,678 IIH patients, 15,567 matched pairs were analyzed. GLP-1 RA use demonstrated significantly decreased NAION risk (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.24-0.93, p = 0.027) and optic atrophy risk (HR 0.78, 95% CI 0.64-0.94, p = 0.009). Time-stratified analyses have demonstrated protective associations across all evaluated time windows. The optic atrophy finding remained significant after Bonferroni correction, while NAION remained significant after false discovery rate correction. Subgroup analysis revealed stronger protective associations in non-diabetic patients (risk ratio 0.53, 95% CI 0.41-0.68) compared to diabetic patients (risk ratio 0.76, 95% CI 0.58-0.99). CONCLUSIONS: GLP-1 RA utilization among IIH patients was associated with a reduced risk of NAION and optic atrophy. These findings align with the proposed pathway linking GLP-1 RA-induced weight reduction to lower intracranial pressure and papilledema reduction in IIH patients; residual confounding cannot be ruled out, and prospective studies are needed to confirm these associations.