Safety of SGLT2 inhibitors for patients with type 2 diabetes: where are we now?

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underused in clinical practice, one of the reasons may be the fear of adverse events which have been emphasized during the first years of use. This comprehensive review aims to give an update on the safety and tolerability profile of SGLT2is. AREAS COVERED: An extensive literature search identified randomized controlled trials, observational cohort studies and pharmacovigilance reports that investigated the safety of SGLT2is in patients with type 2 diabetes (T2D), with or without comorbidities or presenting at-risk conditions. EXPERT OPINION: Some adverse events pointed out initially have been confirmed, especially a higher risk of genital infections, though not the initial fear of urinary tract infections. A euglycemic diabetic ketoacidosis remains exceptional in patients with T2D. Volume depletion is a rare event that may be anticipated. Of note, several severe adverse events that led to warnings by regulatory agencies have not been confirmed in further studies: bone fractures, lower-limb amputations, severe perineal infections, acute renal injury. The safety profile of SGLT2is appears globally reassuring even in special at-risk populations. However, data remain rather scarce in patients with severe comorbidities and in very old or frail people, so that caution use is classically recommended.