Collectively, these newly identified effects of Invokana on heart and kidney disease show significantly enhanced benefits of this medicine. Safety information from recent clinical trials also suggests that the risk of amputation, while still increased with canagliflozin, is lower than previously described, particularly when appropriately monitored. Based on these considerations, we have concluded that the Boxed Warning should be removed.
FDA Boxed Warning
Based on a U.S. Food and Drug Administration (FDA) review of new data from three clinical trials, we have removed the Boxed Warning about amputation risk from the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR) prescribing information.
We required the Boxed Warning in 2017 based on our assessment that the risk of amputations was very serious in relation to the potential benefit of canagliflozin, which was initially approved to be used with diet and exercise to lower blood sugar in adults with type 2 diabetes.
Subsequent FDA reviews of new clinical trial data demonstrated additional heart- and kidney-related benefits, which led to additional approved uses. Specifically:
- In 2018, canagliflozin was approved to reduce the risk of major heart-related events such as heart attack, stroke, or death in patients with type 2 diabetes who have known heart disease; and,
- The amputation risk with canagliflozin remains and is still described in the Warnings and Precautions section of the prescribing information.
- In 2019, it was approved to reduce the risk of end-stage kidney disease, worsening of kidney function, heart-related death, and being hospitalized for heart failure in certain patients with type 2 diabetes and diabetic kidney disease.