Boxed warning on amputation risk removed from canagliflozin label

Recent studies have found a lower risk of leg and foot amputation than previous studies, which in 2017 had prompted the FDA to add the warning to the sodium-glucose cotransporter-2 inhibitor.


The FDA has removed the boxed warning about amputation risk from the prescribing information for canagliflozin (Invokana, Invokamet, Invokamet XR), the agency announced on Aug. 26.

The FDA added the warning to the sodium-glucose cotransporter-2 inhibitor's label in 2017, based on data from two clinical trials that showed an increased risk of leg and foot amputations. Subsequently, additional clinical trials published in 2018 and 2019 led the FDA to approve canagliflozin to reduce the risk of heart attack, stroke, death, end-stage kidney disease, worsening kidney function, and hospitalization for heart failure.

Based on the newly identified benefits of canagliflozin on heart and kidney disease and recent trials' findings of a lower risk for amputation than previously described, particularly when patients are appropriately monitored, the FDA decided to remove the boxed warning, according to the safety announcement.

Among the latest related research, a study of more than 300,000 propensity score-matched adults with type 2 diabetes found that the increased rate of amputation associated with canagliflozin, compared with a glucagon-like peptide-1 receptor agonist, was small. The rate of amputation among adults ages 65 years and older with baseline cardiovascular disease corresponded to a number needed to treat of 556 for one amputation to occur at six months, according to results published online on Aug. 25 by The BMJ.