The U.S. Food and Drug Administration (FDA) recently announced that it would be requiring a new, high-level warning on labels for the type 2 diabetes drug canagliflozin. Sold under the brand names and formulations Invokana, Invokamet, and Invokamet XR, this popular medication for lowering blood sugar levels has been found in new clinical trial data to significantly increase the risk that a patient will require a toe, foot, or leg amputation.
Invokana and Diabetes
Type 2 diabetes is a serious and chronic illness characterized by high blood sugar levels. If let untreated it can lead to complications that include heart disease, nerve damage and pain, kidney damage, and blindness. Patients with type 2 diabetes are encouraged to make lifestyle changes, such as losing weight and being more active, but are also often prescribed medications to help control blood sugar levels.
Invokana is the generic drug canagliflozin, made by Johnson & Johnson and first approved to treat type 2 diabetes in 2013. Since then the medication has continued to be studied in clinical trials. Invokana works by blocking the action of a protein called SGLT2 that reabsorbs sugar from the kidneys and sends it back into the bloodstream. The drug blocks this and allows for greater excretion of sugar.
Risk of Amputations and Boxed Warning
The FDA approved Invokana in 2013, but clinical trials have been ongoing, including two called CANVAS and CANVAS-R. The end results of these two trials showed that patients on Invokana were at an increased risk for needing an amputation when compared to patients in a placebo group who did not receive Invokana. The CANVAS study showed that only 2.8 out of 1,000 patients in the placebo group had leg or foot amputations, while 5.9 out of 1,000 patients in the Invokana group underwent an amputation. The results of the CANVAS-R trial were 4.2 out of 1,000 for the placebo group and 7.5 out of 1,000 for the Invokana group.
Of the patients in the trials who had to have an amputation, most of them involved amputations of a toe or part of the foot. Some patients, however, did have more severe amputations, of the leg both above and below the knee. Some even had multiple amputations, including amputations on both limbs.
Recommendations for Patients and Doctors
The FDA recommends that patients who are taking Invokana should tell their doctors immediately if they develop pain, sores, or infections in their feet or legs. Patients are not encouraged to stop using Invokana without first speaking to their doctors. The FDA also recommends that health professionals treating diabetic patients screen them carefully before prescribing Invokana. They should consider if the patient has any factors that could increase the risk of a future amputation: prior amputations, foot ulcers, neuropathy, and peripheral vascular disease.
Invokana is a relatively new drug, developed in response to the increasing number of cases of type 2 diabetes. The warning about amputations is not the first warning the FDA has issued about Invokana since its 2013 approval. In 2015 the FDA warned that it could increase the risk of diabetic ketoacidosis, a very serious and potentially deadly condition. Warnings have also been issued over the risk of kidney damage and urinary tract infections. If you are being treated for type 2 diabetes, be aware of all the risks of using a medication like Invokana and speak to your doctor about any concerns you have.