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FDA to Review Possible Amputation Risk with Invokana and Invokamet

People with type 2 diabetes should contact their physicians if they notice new pain, sores, or infections on their legs or feet.

The FDA has released a Drug Safety Communication announcing that it is investigating whether J&J’s SGLT-2 inhibitor Invokana (canagliflozin) or combination drug Invokamet (canagliflozin/metformin) might lead to an increased risk of lower limb amputations. This announcement is based on interim data from the “CANVAS” clinical trial focused primarily on Invokana’s heart safety, which unexpectedly found that amputations occurred about twice as often in people taking Invokana compared to those taking placebo – though the overall rates were low in both groups. After an average of 4.5 years, the risk of having an amputation in a given year was equivalent to:

  • 7 out of every 1,000 patients taking 100 mg Invokana

  • 5 out of every 1,000 patients taking 300 mg Invokana

  • 3 out of every 1,000 patients taking placebo

The FDA recommends that people taking Invokana contact their physicians if they notice new pain, tenderness, sores, ulcers, or infections in their legs or feet, but the announcement advises patients not to stop or change any medications without first consulting with a healthcare professional. While we appreciate the FDA’s review of this potential issue, as its priority must be to ensure patient safety first, several scientists and healthcare providers we have spoken with also emphasize that there is no immediate cause for alarm. Notably, this echoes the FDA’s recommendation that nobody should stop their current treatment plan unless any symptoms emerge. As expected, the trial is continuing.

The FDA will provide more updates on this issue when more information is available, as additional data will be needed to definitively show if Invokana/Invokamet increases the risk of amputations or not. There have not been any signs of increased amputation risk in other previous or ongoing clinical trials of Invokana or other SGLT-2 inhibitors (Farxiga and Jardiance), and the independent committee in charge of safety monitoring for the CANVAS trial has recommended that the trial should continue. -ER

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