Interim results from the ongoing CANVAS (Canagliflozin Cardiovascular Assessment Study) clinical trial have found an increased risk of leg and foot amputations associated with the popular diabetes medication.
Interim results from the ongoing CANVAS (Canagliflozin Cardiovascular Assessment Study) clinical trial have found an increased risk of leg and foot amputations associated with the popular diabetes medication, according to a recent FDA Safety Announcement.
The CANVAS trial, aimed at evaluating long-term cardiovascular outcomes of canagliflozin (Invokana, Invokamet), has been ongoing for 4.5 years, with patients being evaluated by an independent data monitoring committee (IDMC). Seven out of every 1000 patients were treated with 100 mg of canagliflozin daily, 5 out of every 1000 treated with 300 mg daily, and 3 out of every 1000 given a placebo. A 1-year analysis found that leg and foot amputations, especially affecting the toes, occurred twice as often in patients treated with canaglifozin as in those treated with placebo.
There has also been a second, similar trial evaluating canagliflozin—the CANVAS-R trial—which has not shown the same risks of increased amputations to date. Patients in the CANVAS-R trial have been evaluated for an average of 9 months. No increase in amputations was seen in 12 other completed clinical trials with canagliflozin either. Full CANVAS trial results are expected in April 2017.
These latest results come on the heels of another recent canagliflozin trial, published in May in Current Medical Research and Opinion, whose findings declared that patients see significant decline in A1C and blood pressure with use of canagliflozin. The results have also led the European Medicines Agency (EMA) to begin their own review on canagliflozin.
“[We have] requested more information from the company to assess whether canagliflozin causes an increase in lower limb amputations and whether any changes are needed in the way this medicine is used in the European Union,” the EMA release stated. The agency anticipates extending the scope of the review to cover all SGLT2 inhibitors, including dapagliflozin and empagliflozin.
Though causation has not been determined, the FDA has begun to alert the public about the potential risk of amputation. Meanwhile, it recommends that healthcare professionals continue following the recommendations on canagliflozin drug labels and monitoring patients for concerning signs and symptoms such as uncontrolled blood sugar levels, blindness, nerve and kidney damage, and heart disease, any new pain or tenderness, sores or ulcers, or infections in their legs or feet. Patients who exhibit any of these are recommended to seek medical advice or report to the FDA MedWatch program. Overall, the IDMC has recommended that the ongoing trials should continue.