Pharmacovigilance study for SGLT 2 inhibitors- Safety review of real-world data & randomized clinical trials

Abstract

Purpose: Sodium-glucose cotransporter 2 (SGLT 2) inhibitors are a novel class of drugs that have emerged as promising therapeutic agents for Diabetes Mellitus, Heart failure as well as chronic kidney disease. Despite their effectiveness, concerns have been raised about the potential side effects of these drugs. To address these concerns, a pharmaco-vigilance study has been designed to evaluate and compare the adverse events reported in clinical trials with those reported in the real-world settings. The study aims to identify any discrepancies between the reported adverse events and assess the safety profile of SGLT2 inhibitors. Methods: We studied diabetic ketoacidosis (DKA), euglycemic DKA, amputation, urinary tract infection (UTI), mycotic genital infection and hypotension associated with empagliflozin, dapagliflozin, canagliflozin and ertugliflozin in RCTs and pharmacovigilance databases. WHO’s VigiBase, FAERS, EMA’s EudraVigilance and DAEN were thoroughly studied to obtain spontaneously reported real-world adverse events. Results: 12 randomized controlled trials (RCTs) for different SGLT2 inhibitors that enrolled 78,802 patients in total were studied for the adverse effects profiles of each drug. Out of the 12 trials included in the current study, UTI was the most reported adverse event in the SGLT2 group, followed by amputation. Out of all the adverse events that were registered in the spontaneous reporting systems, 69,664 were reported for empagliflozin, 51,172 for dapagliflozin, 59,261 for canagliflozin and 1,315 for ertugliflozin. DKA was the most reported adverse event overall. Proportions of composite adverse events were 25.1% in VigiBase, 28.6% in FAERS, 39.1% with EudraVigilance and 55.1% with DAEN. Most of the adverse events were reported by the health care provider. Conclusion: Our study provides comparison of the real world reported adverse events to adverse events reported in the clinical trials studying the efficacy of SGLT 2 inhibitors.