A class action lawsuit has been filed against the makers of Invokana, a diabetes drug that was linked to 22 reports of diabetic ketoacidosis. Suing Merck and its subsidiary Ortho-McNeil-Janssen Pharmaceuticals Inc., the complaint seeks compensation for people who have suffered as a result of taking Invokana.
According to a research published in the journal Diabetes Care, Johnson & Johnson’s diabetes medicine Invokana (canagliflozin) increases the risk of diabetic ketoacidosis (DKA) in type 1 diabetes patients.
The discovery comes almost a year after the FDA warned that Invokana and other diabetic medications might cause DKA, a potentially lethal illness. Meanwhile, the European equivalent of the FDA is looking into the relationship between Invokana and toe amputations.
Dr. Anne L. Peters and colleagues at the University of Southern California Keck School of Medicine conducted a placebo-controlled, double-blind research to see how canagliflozin (an insulin add-on for type 1 diabetes patients) affects glycemic control, weight, and the incidence of DKA.
“People with type 1 diabetes who take an SGLT-2 inhibitor have a higher chance of developing DKA, which seems to be dose-related.”
When cells are deprived of glucose and must rely on fat for energy, chemicals known as ketones are created. This happens when the body doesn’t have enough insulin to utilise glucose as its primary source of energy.
Ketone buildup causes the blood to become more acidic, which may lead to DKA, which can lead to diabetic coma or death.
A new study from the University of Southern California has shown an increased risk of DKA.
At week 18, the incidence of any ketone-related event with canagliflozin was 5.1 percent (100 mg) and 9.4 percent (300 mg) in the Peters trial, whereas significant DKA adverse events requiring hospitalization occurred in 4.3 percent and 6% of the canagliflozin group, respectively. The placebo group saw no ketone-related side effects.
Invokana belongs to the SGLT-2 inhibitor class of medicines. Although the medications are licensed to treat type 2 diabetes, clinicians are permitted to prescribe them for non-FDA approved applications such as type 1 diabetes.
“People with type 1 diabetes who take an SGLT-2 inhibitor are at an elevated risk for DKA, which seems to be dosage related,” said Dr. Peters. “If [canagliflozin] is taken off-label, patients should be thoroughly informed about the risk and ready to monitor ketones during sickness or other stressful situations, and only the lowest dosage of the SGLT-2 inhibitor should be utilized.”
The FDA announced new labeling requirements for SGLT2 inhibitors in December 2015, warning of the risk of ketoacidosis.
In the April 2016 issue of the American Diabetes Association’s Diabetes Care, “Diabetic Ketoacidosis With Canagliflozin, a Sodium–Glucose Cotransporter 2 Inhibitor, in Patients With Type 1 Diabetes” is published.
The CDC is looking into the Invokana connection to amputations.
The European Medicines Agency (EMA), the European counterpart of the FDA, is investigating a potential link between canagliflozin and amputations (mostly of the toe) reported in a medication study.
CANVAS (CANagliflozin cardioVascular Assessment Study) is a post-marketing research trial that aims to evaluate Invokana’s cardiovascular risks in patients with type 2 diabetes, as well as the drug’s overall safety and efficacy. CANVAS trials are taking place around the globe, including in the United States, Europe, Asia, Australasia, and Latin America.
After patients participated in the CANVAS study indicated a rise in lower limb amputations, the EMA began a review of canagliflozin. The relationship between canagliflozin and lower limb amputations has not been verified, according to the FDA, but it is looking into it further.
“The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has requested more information from [Johnson & Johnson] to assess whether canagliflozin causes an increase in lower limb amputations and whether any changes to the way this medicine is used in the EU are required,” the agency said in a statement on April 15.
Frequently Asked Questions
Can Invokana cause ketoacidosis?
Why was Invokana taken off the market?
A: In 2016, the FDA announced that Invokana was linked to an increased risk for blood clots. This is why it was taken off the market and class action lawsuits were filed against its manufacturer.