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

• Topiramate exposure was assessed for first-time urolithiasis risk in Korea. • A nationwide population cohort from Korea was analyzed in this study for five years. • Topiramate exposure was not linked to higher urolithiasis incidence. • Findings support safer clinical decision-making regarding topiramate. • Real-world data suggest no increased stone risk with topiramate use. 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. 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. 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. 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.