In the CANVAS Program trials using canagliflozin, the rates of the 3-point MACE endpoint, the risk of heart failure and the renal composite endpoint were also reduced, albeit with an increased risk of lower extremity amputation and fracture.
Increases in lower extremity amputation and fracture incidence were observed with canagliflozin in CANVAS and this needs further substantiation, though these events were not systematically captured in the EMPA-REG study.