Sodium Glucose Cotransporter 2 Inhibitors, Amputation Risk, and Fracture Risk

Sodium glucose cotransporter 2 (SGLT2) inhibitors are associated with cardiovascular and renal benefits across a broad range of patients, with no increase in total serious adverse events. We evaluated the evidence with respect to amputation and fracture risks for this drug class. Overall, SGLT2 inhibitors are not associated with an increased risk of amputation or fracture in any of the patient populations they have been tested in. The increase in amputation and fracture risks with canagliflozin observed in the CANagliflozin cardioVascular Assessment Study (CANVAS) program was not seen in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial or any study of other SGLT2 inhibitors. Extensive evaluation of amputation and fracture risks suggests that the CANVAS program findings were chance observations rather than real effects.