Acute Renal Failure, Ketoacidosis, and Urogenital Tract Infections with SGLT2 Inhibitors: Signal Detection Using a Japanese Spontaneous Reporting Database.

Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of oral anti-hyperglycemic agents that have been available on the market in Japan since 2014. Although safety information has accumulated alongside the clinical use, the warnings issued by each country based on adverse events associated with the drug are different and examination of the safety of the drug is insufficient. This study examined the safety of SGLT2 inhibitors by using a Japanese spontaneous reporting database and focusing on the cautions issued in each country and the disparities within existing research into the occurrence of the adverse events of acute renal failure (ARF), ketoacidosis, and urogenital tract infections (UTIs). We analyzed data recorded on the Japanese Adverse Drug Event Report database (JADER) between April 2014 and February 2019. We calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) with sex and age as adjustment factors. JADER contained 366,501 cases with the adverse events of interest; 4322 involved SGLT2 inhibitors. The ROR for SGLT2 inhibitors was calculated as 1.0 (95% CI 0.9-1.2) for ARF, 72.2 (95% CI 59.3-87.8) for ketoacidosis, and 14.0 (95% CI 11.0-17.8) for UTIs. Analysis of only subjects receiving treatment for diabetes showed a similar trend. The results suggested a correlation between SGLT2 inhibitors and the onset of ketoacidosis and UTIs, but not between SGLT2 inhibitors and ARF. Further verification of the safety of SGLT2 inhibitors, through continued risk assessments and large-scale clinical studies, are necessary.