FDA Adds New Warnings to SGLT2 Inhibitor Labels

A recent safety review has prompted the U.S. Food and Drug Administration (FDA) to add new warnings about the risks for ketoacidosis and serious urinary tract infections (UTIs) to the labels of sodium glucose co-transporter 2 (SGLT2) inhibitors, according to a drug safety communication from the agency.

In May 2015, the FDA issued a warning about the risk for ketoacidosis with the use of SGLT2 inhibitors, which are indicated for the treatment of type 2 diabetes, and announced that it would continue evaluating the safety issue.

The agency’s review of the FDA Adverse Event Reporting System database from March 2013 to May 2015 identified 73 cases of ketoacidosis in patients with type 1 or type 2 diabetes who were treated with SGLT2 inhibitors.

From March 2013 through October 2014, the FDA also identified 19 cases of urosepsis and pyelonephritis that began as UTIs with the use of SGLT2 inhibitors. All patients were hospitalized, with some requiring admission to an intensive care unit or dialysis to treat kidney failure.

In light of its findings, the FDA advises patients to stop taking their SGLT2 inhibitor and immediately seek medical attention if they have symptoms of ketoacidosis, including nausea, vomiting, abdominal pain, tiredness, and trouble breathing. The agency also recommends that patients look out for signs and symptoms of UTIs, including a feeling of burning when urinating, the need to urinate often or right away, pain in the lower part of the stomach area or pelvis, or blood in the urine.

Healthcare professionals should also be aware of these risks and evaluate for ketoacidosis and UTIs in patients using SGLT2 inhibitors who present with symptoms, the FDA noted.

As a result of the added warnings, the agency is also requiring the manufacturers of SGLT2 inhibitors to conduct a postmarketing study that 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, which include canagliflozin, dapagliflozin, and empagliflozin, are only indicated for treatment of type 2 diabetes and are not currently FDA-approved for use in patients with type 1 diabetes.

The FDA urges healthcare professionals and patients to report adverse events with SGLT2 inhibitors to the agency.

Reference

1. FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. U.S. Food and Drug Administration website. http://www.fda.gov/Drugs/DrugSafety/ucm475463.htm. Updated December 4, 2015. Accessed December 4, 2015.