Dive Brief:
- The Food and Drug Administration is adding a new warning to the prescribing information and patient medication guide for all drugs in the SGLT2 inhibitor class, linking them with increases in the risk of Fournier’s gangrene, a rare but serious infection of the genital area.
- Symptoms include tenderness, redness, and swelling of the genitals or the area from the genitals back to the rectum, along with high fever. Patients taking SGLT2 inhibitors who demonstrate these symptoms should get medical attention immediately, according to the FDA.
- SGLT2 inhibitors are used with diet and exercise to lower blood sugar in adults with Type 2 diabetes, and act by increasing the levels of sugar in the urine.
Dive Insight:
Treating Fournier’s gangrene can include broad-spectrum antibiotics and surgical debridement, but the infection progresses very quickly and can be life-threatening.
The FDA's warning results from observations of 12 cases of the infection in both men and women between March 2013 and May 2018. Though small compared with the 1.7 million people who were prescribed with SGLT2 inhibitors in 2017 alone, the number is significantly larger than the six cases of Fournier’s gangrene found when regulators analyzed more than 30 years of data on other antidiabetic drugs.
The warning will affect SGLT2 inhibitors alone and in fixed-dose combinations. Those include:
- Invokana (canagliflozin)
- Invokamet and Invokamet extended release (canagliflozin and metformin)
- Farxiga (dapagliflozin)
- Xigduo XR (dapagliflozin and metformin extended-release)
- Qtern (dapagliflozin and saxagliptin)
- Jardiance (empagliflozin)
- Glyxambi (empagliflozin and linagliptin)
- Synjardy and Synjardy extended release (empagliflozin and metformin)
- Steglatro (ertugliflozin)
- Segluromet (ertugliflozin and metformin)
- Steglujan (ertugliflozin and sitagliptin).
As clinical and real-world evidence for these widely-used drugs has built up, there have been a number of other warnings added, particularly in small patient populations. In May 2015, the FDA required labels of all SGLT2 inhibitors to warn of the risks of ketoacidosis and the increased risk of serious urinary tract infections.
Johnson & Johnson's Invokana and Invokamet are now required to carry a warning about increased risk of bone fractures and a black box warning for an increased risk of foot and leg amputation. Invokana and AstraZeneca's Farxiga also carry warnings for increased risk of kidney injury.