[About the safety profile of SGLT2 inhibitors]

Since their launch, sodium-glucose cotransporter type 2 inhibitors (SGLT2is) were suspected to be associated with various adverse events. They contributed to delay, as in France, or to restrict the use of this new pharmacological class in clinical practice, despite remarkable results reported in large cardiovascular or renal clinical trials. This article is devoted to three major adverse events that were imputed to SGLT2is : lower-limb extremity amputations, euglycaemic ketoacidosis and acute kidney injuries. In contrast to pharmacovigilance reports that raised suspicion, analysis of all data from the literature, either placebo-controlled trials or retrospective observational cohort studies, led to rather reassuring conclusions. The incidence of amputations does not appear to be increased while cases of acute kidney injury are reduced instead of increased as suspected earlier. Ketoacidosis events are almost doubled with SGLT2is versus comparators, yet their incidence remains extremely low among patients with type 2 diabetes. Of note, this potentially severe complication contributes to the denial of marketing authorization and reimbursement of SGLT2is in the population with type 1 diabetes.