Newly-released studies show Invokana and other type 2 diabetes drugs based on canagliflozin may cause foot and leg amputations at twice the normal rate.
By Laurence Banville
Results from two new clinical trials have prompted regulators at the Food & Drug Administration to warn that the popular type 2 diabetes drug canagliflozin, active ingredient in Invokana, causes an increased risk for leg and foot amputations. The federal agency has told manufacturer Janssen Pharmaceuticals to enhance the drug's labeling materials with a "Boxed Warning" to describe the risk.
Canagliflozin Gets New Black Box WarningCanagliflozin is a powerful new drug that lowers blood sugar levels in patients with type 2 diabetes. Unlike previous treatments, the medications increases the rate at which excess blood sugars are removed from the body by a patient's kidneys.
While untreated cases of diabetes are extremely dangerous, canagliflozin itself has been linked to a number of severe side effects, including diabetic ketoacidosis and kidney failure. Now, the findings of two large clinical trials - dubbed CANVAS and CANVAS-R - have turned up evidence that foot and leg amputations are about twice as common in patients taking canagliflozin than those treated with placebo. Both studies confirmed the link.
Invokana, Invokamet & Invokamet XRInvokana is manufactured by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson. The company is also responsible for Invokamet and Invokamet XR, diabetes medications that both rely in part on the A1C-reducing effects of canagliflozin. All three medications have been associated with limb amputations and will bear a new black box warning to publicize the danger.
CANVAS Trials Find Evidence Of Amputation RiskAs the FDA reported in a Safety Announcement on May 16, 2017, type 2 diabetes patients enrolled in the CANVAS trial, which was designed to investigate the drug's cardiovascular risks, found a wide disparity in amputation rates between canagliflozin and control patients:
- 5.9 amputations per 1,000 patients taking canagliflozin
- 2.8 amputations per 1,000 patients taking placebo
- 7.5 amputations per 1,000 patients taking canagliflozin
- 4.2 amputations per 1,000 patients taking placebo
Patient & Prescriber GuidancePatients currently taking Invokana have been advised to watch for new pains or tenderness in the feet or legs, along with sores, ulcers and infections. Doctors are being told to screen patients, prior to prescription, for risk factors that may increase the likelihood for amputation:
- history of amputation
- peripheral vascular disease
- diabetic foot ulcers