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01 September 2018 – The American Food and Drug Administration (FDA) is warning that cases of a very rare but serious infection of the genitals and area around the genitals have been reported with the class of type 2 diabetes medicines called sodium-glucose cotransporter-2 (SGLT2) inhibitors. This serious rare infection, called necrotizing fasciitis (NF) of the perineum, is also referred to as Fournier’s gangrene. FDA is requiring a new warning about this risk to be added to the prescribing information of all SGLT2 inhibitors and to the patient Medication Guide.
SGLT2 inhibitors are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. SGLT2 inhibitors lower blood sugar by causing the kidneys to remove sugar from the body through the urine. First approved in 2013, medicines in the SGLT2 inhibitor class include canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin (see below for currently FDA-approved SGLT2 inhibitors). In addition, empagliflozin is approved to lower the risk of death from heart attack and stroke in adults with type 2 diabetes and heart disease. Untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease.
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 of 50-79 years (3.3 out of 100,000). However, FDA in the course of their analyses observed events in both women and men.
In five years from March 2013 to May 2018, FDA 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, so there may be additional cases about which FDA is unaware. In 2017, an estimated 1.7 million patients received a dispensed prescription for an SGLT2 inhibitor from U.S. outpatient retail pharmacies. Although most cases of Fournier’s gangrene have previously been reported in men, FDA’s 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.
- 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.
- Read the patient Medication Guide every time you receive a prescription for an SGLT2 inhibitor because there may be new or important additional information about your drug. The Medication Guide explains the benefits and risks associated with the medicine
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.
Health care professionals and patients are also encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:
- Complete and submit the report Online: www.fda.gov/MedWatch/report
- Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
See here the list of currently approved SGLT2 inhibitors:
Brand Name Active Ingredient(s)
Invokamet Canagliflozin and Metformin
Invokamet XR Canagliflozin and Metformin Extended-Release
Xigduo XR Dapagliflozin and Metformin Extended-Release
Qtern Dapagliflozin and Saxagliptin
Glyxambi Empagliflozin and Linagliptin
Synjardy Empagliflozin and Metformin
Synjardy XR Empagliflozin and Metformin Extended-Release
Segluromet Ertugliflozin and Metformin
Steglujan Ertugliflozin and Sitagliptin