FDA warns about ketoacidosis and urinary tract infections with SGLT2 inhibitors

Warnings about ketoacidosis and urinary tract infections will be added to the labels of sodium-glucose cotransporter-2 (SGLT2) inhibitors, the FDA recently announced.

The agency had issued a drug safety communication in May alerting clinicians about the risk of ketoacidosis with these drugs and promising additional review. The new alert and warning are based on that safety review. Between March 2013 to May 2015, 73 cases of ketoacidosis in patients with type 1 or type 2 diabetes taking SGLT2 inhibitors were reported to the agency's Adverse Event Reporting System. There were also 19 cases of life-threatening urosepsis and pyelonephritis that started as urinary tract infections, reported from March 2013 through October 2014. All 19 patients were hospitalized, and a few required ICU admission or dialysis to treat kidney failure, the FDA said.

As a result, the drugs' labels will now carry warnings describing these safety issues. Clinicians should assess for ketoacidosis and urinary tract infections in patients taking SGLT2 inhibitors who present with suggestive symptoms, the FDA's drug safety communication recommended. Patients should be educated to stop taking their SGLT2 inhibitor and seek medical attention immediately if they have any symptoms of ketoacidosis and to be alert for signs and symptoms of a urinary tract infection and seek care if they occur. Ketoacidosis associated with the use of SGLT2 inhibitors can occur even if the blood glucose level is not very high, the FDA noted.

The agency is also requiring manufacturers of SGLT2 inhibitors to conduct a postmarketing study, including analyses of spontaneous postmarketing reports of ketoacidosis for a period of 5 years. Clinicians and patients are encouraged to report adverse events or side effects related to the use of these drugs to the FDA's MedWatch Safety Information and Adverse Event Reporting Program.