Evaluating the Associated Hyperuricemia Risk with Sodium-Glucose Cotransporter 2 Inhibitors: A Sequence Symmetry Analysis Using the Japanese Administrative Claims Database

Hyperuricemia is defined as high uric acid levels within the bloodstream and is commonly associated with gout, type 2 diabetes mellitus, and kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel drugs that prevent glucose reabsorption; additionally, this drug has shown promising results in patients at risk of developing cardiovascular or renal complications by lowering uric acid levels. This study aimed to investigate the association between SGLT2i and hyperuricemia. Here, a self-controlled sequence symmetry analysis using the JMDC administrative claims database (January 2005 to September 2022) consisting of 12396 patients, who were newly prescribed both SGLT2i and hypouricemic agents, was conducted. Trend-adjusted sequence ratios (SR) at intervals of 6, 12, 18, and 24 months were calculated. Significant inverse signals across all intervals were observed between SGLT2i and hypouricemic agents, with the strongest effect observed in the 24-month interval [adjusted SR 0.52 (95% CI 0.49-0.55)]. Significant inverse signals were observed for each of the six types of SGLT2i across all intervals. This indicates that SGLT2i initiation may be associated with a decreased risk of hyperuricemia. Further investigation of the efficacy of SGLT2i is needed in hypothesis-testing designs such as cohort studies.