The FDA has issued a warning for the class of diabetic medications, the sodium-glucose cotransporter-2 (SGLT2) inhibitors, following reports of Fournier’s gangrene, or necrotizing fasciitis of the perineum.
SGLT2 inhibitors are sometimes used to lower blood sugar in diabetics. They work by preventing the body from reabsorbing glucose (sugar), forcing it to be excreted in the urine.
Image from Sirona Biochem
Medscape lists the common drugs in this class:
- Canagliflozin (Invokana, Invokamet, Invokamet XR; Janssen)
- Dapagliflozin (Farxiga, Xigduo XR, Qtern, AstraZeneca)
- Empagliflozin (Jardiance, Glyxambi, Synjardy, Synjardy XR; Boehringer Ingelheim/Eli Lilly)
- Ertugliflozin (Steglatro, Segluromet, Stelujan; Merck)
12 cases had been reported to the FDA, seven of which were men, and five were women, all having had taken an SGLT2 inhibitor. One died, despite treatment.
Last summer, Liu et al published a study in Scientific Reports suggesting an “increased risk of genital infections with SGLT2 inhibitors.”
Symptoms of Fournier’s gangrene may begin with fever, pain, redness or swelling that may occur behind and around the area of the genitalia. Then necrotizing fasciitis ensues when the infection spreads rapidly across (and killing) the fascia, fibrous tissue that surrounds the muscles and organs. Anyone experiencing any of the above symptoms must see a medical provider immediately.
The FDA reports the following:
Patients should seek medical attention immediately if you experience any symptoms of tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell. These symptoms can worsen quickly, so it is important to seek treatment right away.
Health care professionals should assess patients for Fournier’s gangrene if they present with the symptoms described above. If suspected, start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary. Discontinue the SGLT2 inhibitor, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.
Fournier’s gangrene is an extremely rare but life-threatening bacterial infection of the tissue under the skin that surrounds muscles, nerves, fat, and blood vessels of the perineum. The bacteria usually get into the body through a cut or break in the skin, where they quickly spread and destroy the tissue they infect. Having diabetes is a risk factor for developing Fournier’s gangrene; however, this condition is still rare among diabetic patients. Overall published literature about the occurrence of Fournier’s gangrene for men and women is very limited. Publications report that Fournier’s gangrene occurs in 1.6 out of 100,000 males annually in the U.S., and most frequently occurs in males 50-79 years (3.3 out of 100,000).1-3 In our case series, however, we observed events in both women and men.
In the five years from March 2013 to May 2018, we identified 12 cases of Fournier’s gangrene in patients taking an SGLT2 inhibitor. This number includes only reports submitted to FDA* and found in the medical literature,4-6 so there may be additional cases about which we are unaware. In 2017, an estimated 1.7 million patients received a dispensed prescription for an SGLT2 inhibitor from U.S. outpatient retail pharmacies.7Although most cases of Fournier’s gangrene have previously been reported in men, our 12 cases included 7 men and 5 women. Fournier’s gangrene developed within several months of the patients starting an SGLT2 inhibitor and the drug was stopped in most cases. All 12 patients were hospitalized and required surgery. Some patients required multiple disfiguring surgeries, some developed complications, and one patient died. In comparison, only six cases of Fournier’s gangrene (all in men) were identified in review of other antidiabetic drug classes over a period of more than 30 years.
This is a developing story.