FDA Adverse Event Analysis Links Invokana, Other SGLT2 Inhibitors to Acute Kidney Failure

Published on October 30, 2017 by Sandy Liebhard

A recently-published analysis involving the U.S. Food & Drug Administration’s (FDA) adverse event database suggests that a new class of Type 2 diabetes drugs called SGLT 2 inhibitors may be associated with acute renal failure, a complication alleged in a growing number of lawsuits involving Invokana and Invokamet.

What did the Study Reveal?

To determine the relationship between this medication class and acute renal failure, researchers writing in Nutrition, Metabolism & Cardiovascular Diseases evaluated 18,915 adverse event reports involving SGLT2 inhibitors that had been logged with the FDA’s database between 2013 and September 2016.

Their analysis revealed the following:

• 6.5% of the adverse event reports involved acute kidney failure.
• SGLT2 inhibitors were were judged to be the primary or secondary cause of acute renal failure in 96.8% of the cases.
• 42% of the cases led to hospitalization or prolongation of hospitalization and 16 ended in death.

Medications in the SGLT 2 inhibitor class were also associated with a higher proportion of acute renal failure reports compared with other Type 2 diabetes drugs.

Canagliflozin (the active ingredient in Invokana and Invokamet 7.3%) was involved in more cases of acute kidney failure compared to empagliflozin (Jardiance, 4.7%) and dapagliflozin (Farxiga 4.8%).

The study also suggested that male sex, obesity, and use of concomitant diuretics or angiotensin-converting enzyme inhibitors could be predictors for acute renal failure among patients taking SGLT2 inhibitors.

Other Side Effects Linked to SGLT 2 Inhibitors

Invokana was approved by the FDA in March 2013 and was the first SGLT 2 inhibitor to be cleared for sale in the U.S.  Several other drugs in this class have since come to market, including:

• Invokamet (canagliflozin and metformin)
• Farxiga (dapagliflozin)
• Xigduo XR (dapagliflozin and metformin extended-release)
• Jardiance (empagliflozin)
• Glyxambi (empagliflozin and linagliptin)

SGLT 2 inhibitors work by preventing the absorption of glucose by the kidneys, thereby allowing its elimination from the body through urine. While the medications are effective in treating Type 2 diabetes, they are not without side effects.

In September 2015, the FDA announced that new information regarding a possible increased risk of bone fractures would be added to the labels for Invokana and Invokamet. In December of the same year, new warnings regarding diabetic ketoacidosis and serious urinary tract infections were added to the labels of all SGLT2 inhibitors.

Existing kidney warnings included in the prescribing information for Invokana, Invokamet, Farxiga, and Xigduo XR were strengthened in June 2016, after those medications were linked to more than 100 reports of acute kidney injury.

In May, the labels for Invokana and Invokamet were modified with a new black box warning – the FDA’s strongest possible safety alert – regarding a risk of leg and foot amputations.

Invokana Lawsuits

More than 800 lawsuits have been filed on behalf of plaintiffs who allegedly suffered life-threatening side effects associated with Invokana and Invokamet, including diabetic ketoacidosis, kidney failure and other renal complications, heart attacks and strokes, and amputations.

The majority of these cases are undergoing coordinated pretrial proceedings in the U.S. District Court, District of New Jersey. Plaintiffs claim that Johnson & Johnson and Janssen were aware of the serious and potentially life-threatening risks allegedly associated with Invokana and Invokamet, but concealed this information from the public and failed to provide appropriate safety warnings to doctors and patients.