Final results from CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus) showed that leg and foot amputations occurred about twice as often in patients treated with canagliflozin vs. placebo. Health care professionals are advised that before prescribing canagliflozin, they consider factors that may predispose patients to the need for amputations, such as: history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Patients should be monitored for signs and symptoms and discontinue canagliflozin if these complications occur.
In 2016, the MHRA had issued a similar warning based on preliminary findings from the CANVAS trial- which was still ongoing at the time- and had issued advice to minimise this risk.