Canagliflozin side effects can include an increased risk of lower limb amputation, warns the U.S. Food and Drug Administration (FDA).

Invokana and Invokamet are among the drugs that contain canagliflozin as their active ingredient. These can cause canagliflozin side effects.  

The medications belong to a class of drugs known as sodium-glucose cotransporter-2 (SGLT2) inhibitors that include:

• Invokana (canagliflozin)
• Invokamet (canagliflozin metformin)
• Invokamet XR (canagliflozin and metformin hydrochloride extended-release)

FDA-approved in 2013, these drugs help maintain steady blood sugar levels by redirecting excess glucose away from the bloodstream and out of the body through the urine. Canagliflozin side effects are seen in a wide range of body systems. The drugs have been linked to increased risks of kidney failure, ketoacidosis, dangerous urinary tract infections, flesh-eating bacteria of the genitals and amputations. The FDA is looking into reports that canagliflozin side effects also might include an increased risk of acute pancreatitis.

Canagliflozin Side Effects Include Amputations

Two clinical trials found that patients taking Invokana, Invokamet or Invokamet XR needed leg or foot amputations at twice the rate of patients not on the drugs.

The clinical trials, known as CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-A (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus), prompted the FDA to order a black box warning regarding the risk of amputations.

The FDA’s black box warning is the most serious warning and is only used for medications that can cause side effects that could result in severe injury or death. Johnson & Johnson added the black box warning about amputations risks after the order from the FDA in May 2017.

According to the CANVAS clinical trials, amputations of a big toe or the middle of the foot were most often needed. In some patients, amputations involved a leg that needed amputating either above or below the knee. In the worst cases, patients needed more than one amputation, sometimes affecting both legs or feet.

Another study by Peter Ueda, MD, Ph.D. of Karolinska University Hospital in Stockholm, Sweden, confirmed the results of CANVAS. According to an article by TCTMD, the BMJ published the study’s results in November 2018 that found canagliflozin side effects included a risk of lower limb amputations that was twice that of patients taking a different medication known as a glucagon-like peptide 1 (GLP1) receptor agonist.

In Ueda’s study, the majority of patients suffered from the need of toe or metatarsal (middle of the foot) amputations. The rate of amputation was greater among patients who had a history of peripheral artery disease and those who had undergone a previous amputation of a lower limb. Peripheral artery disease is a condition marked by poor blood circulation because of narrowed blood vessels that reduce the flow of blood to the limbs.

Ueda was quoted by TCTMD as saying the risk of amputation is greater for patients who also suffer from foot ulcers.

Janssen Pharmaceuticals and its parent company, Johnson & Johnson, are defendants in hundreds of lawsuits filed by patients who say did not receive warnings of an increased risk of amputations and other dangerous canagliflozin side effects.