The Food and Drug Administration is sending a public alert, warning that an increase in leg and foot amputations has been reported in patients in an ongoing clinical trial of canagliflozin, a diabetes drug with the brand names Invokana and Invokamet.
Though the FDA says it hasn’t yet determined whether canagliflozin actually increases the risk of these amputations, it considers the reports a “new safety issue” and it’s investigating. The agency promises an update on this after it obtains more information.
Canagliflozin is a prescription medicine used with diet and exercise to lower blood sugar in adults with type 2 diabetes. It belongs to a class of drugs called sodium-glucose cotransporter-2 (SGLT2) inhibitors. Canagliflozin lowers blood sugar by causing the kidneys to remove sugar from the body through the urine. It is available as a single-ingredient product under the brand name Invokana and also in combination with the diabetes medicine metformin under the brand name Invokamet.
Amputations twice the rate
The clinical trial in which these problems were observed is the Canagliflozin Cardiovascular Assessment Study (CANVAS). The increased risk of leg and foot amputations was identified by the trial’s independent data monitoring committee . It reported that amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with a placebo. An interim analysis showed that over a year’s time, the risks of amputation for patients in the trial were equivalent to:
- 7 out of every 1,000 patients treated with 100 mg daily of canagliflozin
- 5 out of every 1,000 patients treated with 300 mg daily of canagliflozin
- 3 out of every 1,000 patients treated with placebo
Even with this information, the data monitoring committee has recommended that the CANVAS trial continue. Patients in the CANVAS trial have been followed for an average of 4.5 years to date.
The monitoring committee reports that a second, similar trial evaluating canagliflozin, the CANVAS-R trial, has not shown the same risks of increased leg and foot amputations to date. Patients in the CANVAS-R trial have been followed for an average of 9 months.
The FDA cautions patients not to stop or change their diabetes medicines without first talking to their health care professional. Patients taking these drugs should notify their health care professionals right away if they notice any new pain or tenderness, sores or ulcers, or infections in their legs or feet.