Association of Sodium-Glucose Cotransporter-2 Inhibitors With Fournier Gangrene: A Disproportionality Analysis Using the Japanese Adverse Drug Event Report Database.

Abstract

This study investigated the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and Fournier gangrene (FG), analyzing additional risk factors using pharmacovigilance data. Data were extracted from the Japanese Adverse Drug Event Reporting (JADER) database (April 2014-August 2024), encompassing 914,713 adverse event reports, including 5770 involving SGLT2 inhibitors. Among 40 identified FG cases (0.69% of SGLT2 reports), empagliflozin showed the strongest association (reporting odds ratio = 78.62) and canagliflozin the weakest. Male patients demonstrated significantly higher FG risk than female patients (P = 0.004), particularly with tofogliflozin. No significant correlation existed between obesity and FG occurrence. Onset timing varied widely (12-1515 days). Limitations include potential data incompleteness inherent to spontaneous reporting systems, limited sample size, and inability to establish definitive causality. All 5 SGLT2 inhibitors were associated with FG, with empagliflozin carrying the highest risk. Male patients exhibited elevated susceptibility. Continuous monitoring throughout treatment is essential. Further clinical trials are warranted to clarify causal relationships.