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SGLT-2 Inhibitors’ Association with Fournier Gangrene

Dec 10, 2019
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Maya Rudolph, Florida A&M University, College of Pharmacy & Pharmaceutical Sciences, PharmD Candidate

While rare, Fournier gangrene infections can worsen rapidly and have serious consequences. 

Fournier gangrene is a rare, life-threatening bacterial infection of the skin that involves the tissues, surrounding muscles, nerves, and blood vessels of the external genitalia, perianal region, and perineum (the area between the anus and scrotum for men; between the anus and vulva for women). Bacteria, spreading from a skin wound or injury, destroys the tissue leading to a necrotizing infection due to a lack of blood flow or bacterial infection. Fournier gangrene is more common in men. Health conditions, such as diabetes, are a possible risk factor and make patients most likely to contract the infection. This infection is rare in patients with diabetes, but due to infections thriving off high blood glucose levels, the risk is still significant.


Recently, patients with type 2 diabetes using sodium-glucose cotransporter (SGLT)2 inhibitors have shown an increased risk for Fournier gangrene. SGLT-2 inhibitors are commonly known for adversely causing glycosuria, which leads to urinary tract infections and urogenital infections, consecutively increasing the risk of Fournier gangrene. Since the gastrointestinal tract already surrounds the perineum, the glycosuria-enhanced growth of urogenital flora may provide an ideal environment for this infection to grow.

The U.S. Food and Drug Administration (FDA) is warning patients with type 2 diabetes receiving SGLT-2 inhibitors to use with caution due to the reported cases of Fournier gangrene. FDA investigators apart from the Adverse Event Reporting System are requiring a new warning about the risk to be added to the prescribing information. Between March 1, 2013, and January 31, 2019, the FDA has identified 55 cases of Fournier gangrene in patients with diabetes taking SGLT-2 inhibitors.

SGLT-2 inhibitors, approved by the FDA in 2013, are used to lower blood glucose in patients with type 2 diabetes. SGLT-2 inhibitors inhibit SGLT-2 co-transporters, reducing the reabsorption of filtered glucose in the kidneys, and subsequently increasing urinary glucose excretion, in exchange for lowering blood glucose levels. Drugs in this class include canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT-2 inhibitors are good for patients wanting to lose weight and useful in the reduction of cardiovascular issues. Some common adverse effects associated with SGLT-2 inhibitors are genital mycotic infections, urinary tract infections, and polyuria. This class of anti-diabetic drugs has proven to be effective in lowering HbA1C.

From the findings of the FDA, the 55 cases of Fournier gangrene patients’ ages ranged from 33 to 87 years old, with 39 men and 16 women. The therapy duration of the SGLT-2 inhibitors was extended from 5 days to 49 months. Surgical debridement was performed in all patients who were critically ill. Complications amongst the patients included diabetic ketoacidosis (n=8), sepsis or septic shock (n=9), and acute kidney injury (n=4). Other serious complications that occurred in patients involved fecal diversion surgery (n=8), developing necrotizing fasciitis of a lower extremity leading to amputation (n=2), gangrenous toes requiring bypass procedure (n=1). Observation detected three deaths amongst the patients.

The FDA studied 19 other Fournier gangrene cases related to other anti-diabetic medication classes. The years of research ranged from 1984 to January 31, 2019. The medications in the various drug classes were: metformin (n=8), insulin glargine (n = 6), short-acting insulin (n = 2), sitagliptin plus metformin (n = 2), and dulaglutide (n = 1). Patients’ ages ranged from 42 to 79 years old, with 12 men and seven women. Two deaths were reported during the years.

If patients who are receiving SGLT-2 inhibitors begin to experience signs of fever, tenderness, redness, or swelling of the genital area, they should seek medical attention immediately. Signs and symptoms of Fournier gangrene can worsen fast; thus, it is vital to seek medical professionals.

Healthcare providers and clinicians should be aware of this fatal but rare infection when initiating SGLT-2 inhibitors into therapy for patients with diabetes. If Fournier gangrene is suspected in patients, broad-spectrum antibiotics should be started immediately. Surgical debridement may be necessary for eradicating the infection. The SGLT-2 inhibitor should be discontinued. An appropriate selection of alternative therapy should be initiated. Clinicians should closely monitor blood glucose levels.

Practice Pearls:

  • Fournier gangrene has been identified as a safety concern in patients with diabetes receiving SGLT-2 inhibitors.
  • FDA warns prescribers of the rare but serious infection. 
  • Fournier gangrene symptoms can worsen quickly.

Bersoff-Matcha, Susan J., et al. “Fournier Gangrene Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases.” Annals of Internal Medicine, 7 May 2019, annals.org/aim/article-abstract/2732837/fournier-gangrene-associated-sodium-glucose-cotransporter-2-inhibitors-review-spontaneous?doi=10.7326/M19-0085.

Center for Drug Evaluation and Research. “Warning: Infection of Genital Area with SGLT2 Inhibitors for Diabetes.” U.S. Food and Drug Administration, FDA, www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrences-serious-infection-genital-area-sglt2-inhibitors-diabetes.

“Postmarketing Data Support Fournier Gangrene Link with SGLT2 Inhibitors.” Diabetes.medicinematters.com, 7 May 2019, diabetes.medicinematters.com/sglt2-inhibitors/adverse-effects/postmarketing-data-support-fournier-gangrene-link-with-sglt2i/16698404.

Maya Rudolph, Florida A&M University, College of Pharmacy PharmD Candidate