The CANVAS program detected a 2-fold increased risk of lower limb amputation in patients treated with canagliflozin compared with those with placebo. This adverse effect was not confirmed in the CREDENCE trial. Moreover, randomized controlled trials with other agents in this class, dapagliflozin and empagliflozin, did not detect increased risk of amputation. Observational studies, cohort studies, and pharmacovigilance reports with sodium-glucose cotransporter 2 inhibitor (SGLT2i) have reported conflicting results. Whether this adverse event is a drug effect specific to canagliflozin, or a SGLT2i class effect, remains controversial. Until more evidence emerges, clinicians should avoid using SGLT2i, especially canagliflozin, in patients with previous amputations or existing foot ulceration.
Keywords: amputations; canagliflozin; dapagliflozin; empagliflozin; sodium-glucose cotransporter 2 inhibitors.