FDA Mandates New Study and Warnings on Labels for SGLT2 Inhibitors

Washington, DCA review by the US Food and Drug Administration (FDA) of specific class of type 2 diabetes medicines called sodium-glucose cotransporter-2 (SGLT2) inhibitors, has resulted in the agency adding warnings to the labels concerning the risks for serious urinary tract infections (UTIs) too much acid in the blood. Both these conditions can result in hospitalization.

The FDA issued initial warnings about the risks for ketoacidosis and UTIs associated with SGLT2 inhibitors canagliflozin (Invokana), dapagliflozin (Forxiga), and empagliflozin (Jardiance) in May 2015.

During a review of the FDA Adverse Event Reporting System (FAERS) database from March 2013 to May 2015, the agency identified 73 cases of ketoacidosis in patients with type 1 or type 2 diabetes treated with SGLT2 inhibitors. Symptoms of ketoacidosis include nausea, vomiting, abdominal pain, tiredness, and trouble breathing.

Further, the FDA also identified 19 cases of life-threatening blood infections (urosepsis) and kidney infections (pyelonephritis) that started as urinary tract infections with the SGLT2 inhibitors. All 19 patients were hospitalized, a few of whom required admission to an intensive care unit or dialysis in order to treat kidney failure.

As a result, the FDA added new Warnings and Precautions to the labels of all SGLT2 inhibitors, describing these two safety issues, and to provide prescribing and monitoring recommendations.

In addition to the new warnings, the FDA is requiring the makers of SGLT2 inhibitors to conduct a postmarketing study. This enhanced pharmacovigilance study requests that manufacturers perform analyses of spontaneous postmarketing reports of ketoacidosis in patients treated with SGLT2 inhibitors, including specialized follow-up to collect additional information, for a period of 5 years.

SGLT2 inhibitors are prescribed for use with diet and exercise to lower blood sugar in adults with type 2 diabetes.