Exposure to topiramate may not increase the risk of urolithiasis: A nationwide cohort study.

Background and purpose: Although topiramate is mechanistically linked to an increased risk of urolithiasis, real-world evidence remains conflicting. This study aimed to evaluate the risk of a first-time episode of urolithiasis associated with topiramate exposure in the Korean population. Methods: Using the Korean National Health Insurance Service-National Sample Cohort, we identified participants from the 2015 national health screening. After excluding individuals with a prior diagnosis of urolithiasis, we performed 1:4 propensity score matching between patients with and without topiramate exposure. Matching variables included age, sex, body mass index, comorbidities, and a history of gout. Participants were followed longitudinally, and the risk of urolithiasis was assessed using Kaplan-Meier analysis and Cox proportional hazards regression. Results: The final cohort included 1,560 patients exposed to topiramate and 6,240 matched controls who were followed for five years. During the follow-up period, urolithiasis was diagnosed in 47 patients (3.0%) in the topiramate group and 170 patients (2.7%) in the control group. The risk of developing urolithiasis was not significantly different between the two groups (p = 0.545). Furthermore, subgroup analyses stratified by current use or the cumulative duration of topiramate exposure also showed no significant associations. Conclusions: In this large, nationwide cohort, topiramate exposure was not associated with an increased risk of urolithiasis. Our findings suggest that in a real-world setting, the risk may not be as significant as suggested by its pharmacological mechanism.