Fatal Infection Identified as Rare Side Effect of SGLT2 Inhibitors Such as Canagliflozin

The American College of Physicians report that physicians prescribing a sodium-glucose contrasporter-2 (SGLT2) inhibitor for type 2 diabetes should be on the alert for symptoms of Fournier gangrene, a rare form of necrotizing bacterial infection that affects soft tissue in the genitals. A newly identified safety concern in patients receiving SGL2 inhibitors, Fournier gangrene can be deadly. The findings are the result of a review of spontaneous post marketing cases published in the Annals of Internal Medicine.

The most common adverse reactions identified with SGLT2 inhibitors in clinical trials were genital mycotic and urinary tract infections, but the SGLT2 inhibitor class can also be associated with Fournier gangrene. Researchers from the U.S. Food and Drug Administration reviewed adverse event reports to describe and compare reported cases of Fournier gangrene in patients receiving SGLT2 inhibitors versus other antiglycemic agents.

The researchers identified 55 cases among patients receiving SGLT2 inhibitors during the 6 years since canagliflozin received U.S. marketing approval in March 2013. Serious complications and death are likely if Fournier gangrene is not recognized immediately and surgical intervention is not carried out within the first few hours of diagnosis. All patients in the case series were hospitalized, some required several surgeries, some had complications, and three died as a result of Fournier gangrene.

The researchers found only 19 Fournier gangrene cases in 35 years among patients receiving other classes of antiglycemic agents. According to the researchers, awareness of the association between Fournier gangrene and SGLT2 inhibitor use may be an important factor in an informed prescriber-patient discussion regarding appropriate diabetes therapy.

SGLT Inhibitors

The sodium glucose cotransporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin represent a novel class of medications to manage type 2 diabetes through urinary excretion of glucose. These drugs block glucose reabsorption by the kidneys to increase glucosuria. These drugs provide hemoglobin A1C reduction, promote weight loss, and remain hypoglycemic-neutral when not used in combination with insulin or secretagogues. Canagliflozin and empagliflozin have shown cardiovascular benefit. The potential to reduce the risk of cardiovascular death in patients with type 2 diabetes, along with the benefit of weight reduction, makes these new agents useful tools for the primary care provider. Canagliflozin was the first of this class approved by the FDA for the treatment of type 2 diabetes. Consequently, stronger warnings have been issued by the FDA for canagliflozin (Invokana).

Drug History

The drug was developed by Mitsubishi Tanabe Pharma and is marketed by Janssen (division of Johnson & Johnson). It was approved by the FDA on March 29, 2013, and became the first SGLT inhibitor in the United States.