Association between Proton Pump Inhibitor Use and Incident Gout: A Population-Based Cohort Study

Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders, but their association with gout remains uncertain.We evaluated the association between PPI use and incident gout in a retrospective cohort using data from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2019.Adults with prior gout or hyperuricemia were excluded.PPI users were defined as individuals recently diagnosed with gastroesophageal reflux disease or peptic ulcer disease who were prescribed a PPI, whereas non-users had no PPI prescriptions or GERD/PUD diagnoses during the study period.The primary outcome was a gout claim occurring at least 30 days after the index date.Inverse probability of treatment weighting and weighted multivariable Cox proportional hazards models were applied.Among 543,815 participants, 455,243 were PPI users and 88,572 were non-users.During follow-up, 39,905 and 3,381 gout events occurred among PPI users and non-users, with incidence rates of 14.04 and 5.34 per 1,000 person-years, respectively.PPI use was associated with a higher hazard of incident gout after weighting and multivariable adjustment (adjusted hazard ratio [HR], 1.873; 95% confidence interval [CI], 1.831-1.915).The association persisted when gout was defined by at least two diagnostic claims (adjusted HR, 1.811; 95% CI, 1.756-1.868)or by a diagnosis accompanied by gout-related medication use (adjusted HR, 1.513; 95% CI, 1.437-1.593).In this large Korean claims-based cohort, PPI use was associated with a higher hazard of incident gout, with the association remaining in the same direction across more specific outcome definitions, although effect estimates were lower.