Invokana, generically known as canagliflozin, and Invokamet, a combination drug of canagliflozin and metformin, are part of a class of type-2 diabetes medications known as sodium glucose co-transporter 2 (SGLT2) inhibitors.

Through a recent study known as the CANVAS program, these drugs were reportedly found to increase canagliflozin amputation risk, according to the U.S. Food and Drug Administration (FDA).

According to a MedPageToday article, the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial gave the FDA heart risk information needed to initially approve the diabetes drug. The drug oversight agency required a post-market follow-up study, however. The decision was made not to follow the same group of patients.

The post-market CANVAS-R study enrolled 10, 142 patients globally from 30 countries being seen at 667 different centers. All enrollees had type-2 diabetes and had high cardiovascular risk factors.

At least 65 percent of the patients already had a medical history of heart disease and the remainder had developing signs. The average age of the involved population was slightly over 60 years of age and a third of them were women.

Dr. Bruce Neal of the University of New South Wales in Sydney, Australia headed up this post-market study which produces data then combined with the assistance of six other scientific researchers in the CANVAS program.

The statistical canagliflozin amputation risk drew upon this combined data to form conclusions that were significant enough to get the attention of the FDA.

The study found that out of every 1,000 patients, approximately six underwent amputation of a toe or metatarsal–a rate almost double that seen in patients taking a placebo.

The CANVAS-R study revealed that a larger number of patients experienced canagliflozin amputation risk for other types of amputations.  Out of every 1,000 patients taking the drug in this follow-up, 7.5 patients lost a toe, part of their foot, or even part of their leg during one year. This compared to 4.2 patients who underwent amputation while taking the placebo.

The identified risk was reportedly more pronounced according to combined data in patients with a history of foot ulceration related to their diabetes, previous partial amputations, the presence of heart disease or high risk factors, nerve damage in the extremities, or compromised blood vessels in the legs with narrowing or blockage.

Although type-2 diabetics are already at risk for amputation, the FDA was concerned enough by this information that a boxed warning was ordered on May 16, 2017.

The FDA warns the medical community that diabetic patients already have an elevated risk for amputations due to diabetes in general. So, the potential link between canagliflozin and amputations is particularly concerning given that the drug is supposed to help treat diabetes symptoms.

Diabetics have a higher risk of amputations than the general community because diabetes can damage the nervous system. This can cause a patient to lose nerve feeling, so they may not notice if they have suffered an injury. This nerve damage occurs most often in peripheral nerves, like in the limbs, which are often subject to bumps and bruises.

Unfortunately, diabetic nerve damage is rendered even more damaging, as diabetic patients often have difficulty healing from wounds. Medical News Today notes that diabetics often have reduced blood flow to the feet. This reduced blood flow is part of why diabetics have difficulty healing from wounds. 

According to Medical News Today, circulation issues including peripheral artery disease, which is linked to diabetes, may prevent ulcers and wounds from healing. These conditions increase the possibility that an injury can become severe, which could lead to infection. A bad infection or a wound that does not heal may require an amputation, because the tissue may die.

According to Medical News Today, the American Diabetes Association reported that globally, a person loses a limb to diabetes-related complications every 30 seconds. Experts recommend that action should be taken early to ensure that a wound on a limb, particularly on a leg, does not progress.

Patients that are taking this drug need to be aware and express their concerns to their prescribing physicians before removing any drug from their treatment regimen. If you experienced increased canagliflozin amputation risk by taking Invokana, Invokamet, or Invokamet XR and lost any part of a toe, foot or leg, you may have a legal claim.