The increased amputation risk associated with the type 2 diabetes drug Invokana was not seen in patients taking Jardiance, a medication in the same class, according to a new study published in the journal Diabetes Care.
In May 2017, the FDA issued a Safety Communication alerting the public that based on new data from two large clinical trials, the agency had concluded that the medicine canagliflozin (the active ingredient in the type 2 diabetes drugs Invokana, Invokamet and Invokamet XR) causes an increased risk of leg and foot amputations. As a result, the FDA required the safety labels of all medications containing canagliflozin to include a boxed warning describing the risk. A boxed warning – also called a black box warning – is the most serious type of warning the agency issues.
The studies showed leg and foot amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with a placebo. One study followed patients over the course of a year and found that 5.9 out of every 1,000 patients taking canagliflozin required amputations compared to 2.8 out of every 1,000 patients taking a placebo. The second study found that 7.5 out of every 1,000 patients taking canagliflozin had an amputation compared to 4.2 out of every 1,000 patients treated with a placebo.
The amputations most often affected the toe and middle of the foot; however, amputations involving the leg – both below and above the knee – were also seen. Some patients had more than one amputation, with some involving both limbs.
European drug regulators, fearful that the risk would be similar for other drugs in same class, called SGLT2 inhibitors, required amputation warnings on all SGLT2 inhibitors. The FDA refrained from including other drugs in the class.
But the new study led by Silvio Inzucchi, MD, of Yale University, found no evidence of an increased risk of lower-limb amputation with Jardiance compared to placebo. Jardiance contains the active ingredient empagliflozin. The rate was 6.5 amputations per 1,000 patient-years in both the empagliflozin and the placebo groups.
FDA Safety Communication