Study Suggests Acute Kidney Injury Warning for Invokana and Similar Diabetes Drugs Was Unwarranted

Several years after federal regulators required a label update about the risk of acute kidney injury from Invokana and other similar diabetes drugs, a new study raises question about the warnings.

In a study published this month in the Canadian Medical Association Journal (CMAJ), researchers indicate the side effects of a class of diabetes drugs known as sodium-glucose cotransporter-2 (SGLT2) inhibitors appear less likely to cause acute kidney injury among older patients than other types of diabetes drugs, such as Onglyza, and say they do not believe the FDA’s 2016 label warning update is warranted.

Invokana (canagliflozin) was the first SGLT-2 inhibitor introduced to the market, which was approved in March 2013, and quickly became a blockbuster treatment. The medication works in a unique way, impacting some normal kidney functions to help remove glucose from the body through urine.

Similar drugs that are part of the same class followed, including Invokamet, Invokamet XR, Farxiga, Xigduo XR, Qtern, Jardiance, Glyxambi, Synjardy, Synjardy XR, Steglatro, Segluromet and Steglujan.

In June 2016, the FDA required additional label warnings about the link between kidney risks and Invokana and other drugs from its class, indicating the medications may increase the risk of acute kidney injury and other severe health problems.

In this latest study, researchers conducted a population-based retrospective cohort study in Ontario, Canada, involving nearly 40,000 patients age 66 or older who were new users of either an SGLT2 inhibitor, like Invokana, or a dipeptidyl peptidase-4 (DPP4) inhibitor, like Onglyza.

According to their findings, those given drugs like Invokana had a lower 90-day risk of being hospitalized for acute kidney injury (AKI), with the rate of kidney injury being about half of those suffered by patients taking DPP4 inhibitors.

“In routine care of older adults, new use of SGLT2 inhibitors compared with use of DPP4 inhibitors was associated with a lower risk of AKI,” the researchers concluded. “Together with previous evidence, our findings suggest that regulatory warnings about AKI risk with SGLT2 inhibitors is unwarranted.”

Invokana Health Risks

Beyond kidney problems, Invokana and similar drugs have been linked to a number of other health problems in recent years.

In December 2015, the FDA required Johnson & Johnson to add new diabetic ketoacidosis warnings to Invokana and similar drugs, indicating that the medications increase the risk of this serious condition, which typically results in the need for emergency treatment to avoid life-threatening injury. Prior to the update, the warnings failed to alert consumers about the importance of seeking immediate medical attention if they experience symptoms like abdominal pain, fatigue, nausea, respiratory problems or vomiting.

In May 2017, FDA required new warnings about the Invokana amputation risks, adding information to the drug label about the increased incidence of leg, foot and toe amputations. That warning was only required for Invokana, and manufacturers of other SGLT-2 inhibitors have suggested that Invokana leg and foot amputation problems were unique to that drug, maintaining that the same risks were not seen among users of their medications.

In addition,  in August 2018 the FDA issued a warning linking the drugs to serious flesh-eating infections around the genitals, known as necrotizing fasciitis of the perineum, or Fournier’s gangrene.

Johnson & Johnson and Janssen have faced several thousand other Invokana lawsuits, which allege users and the medical community were not provided adequate warnings at the time the drug was first introduced. The makers of other diabetes drugs from the same class, including Farxiga and Xigduo XR, have also faced similar lawsuits; though most have been filed against the makers of Invokana.