Postmarketing data support Fournier gangrene link with SGLT2 inhibitors
medwireNews: Fournier gangrene remains very rare, but is more common in people using sodium-glucose cotransporter (SGLT)2 inhibitors compared with other diabetes medications and has severe consequences, shows research.
The analysis of postmarketing data, reported in the Annals of Internal Medicine, reveals 55 cases in patients using SGLT2 inhibitors over a nearly 6-year period between March 2013 and January 2019. By contrast, there were only 19 cases in patients using other diabetes medications over a much longer 35-year period.
Susan Bersoff-Matcha and FDA colleagues from Silver Spring, Maryland, USA, note that SGLT2 inhibitor treatment results in glycosuria, which raises the risk for urinary tract and urogenital infections, which in turn are thought to increase risk for Fournier gangrene.
“In addition, because the perineum already is colonized with organisms from the gastrointestinal tract, the enriched environment provided by glycosuria-enhanced growth of urogenital flora may provide the ideal milieu for [Fournier gangrene],” they say.
However, urinary tract infection was reported in just two of the 55 patients in this study, and whether it “was an important inciting event in the remaining cases is unclear,” the team adds.
Cases of Fournier gangrene occurred in patients using all SGLT2 inhibitors apart from ertugliflozin, which the researchers attribute to the latter’s relatively short length of time on the market – just over a year at the time of the analysis.
They stress that Fournier gangrene remains overall rare, “accounting for less than 0.02% of annual hospitalizations in the United States.”
The 39 men and 16 women who developed Fournier gangrene were aged between 33 and 87 years and they developed the condition between 5 days and 49 months after starting SGLT2 inhibitor treatment.
Three patients died, and all surviving patients required hospitalization, for between 5 and 51 days. Although the number of operations was not always stated, at least 25 patients underwent more than one surgical procedure, with one needing 17 operations. Other severe complications were common, with eight cases of diabetic ketoacidosis, nine of sepsis or septic shock, and four of acute kidney injury.
Discharge destination was recorded for only six of the surviving patients, all of whom were transferred to a rehabilitation facility. But the researchers “suspect that almost no patient could return home immediately and that total inpatient time was much longer.”
Bersoff-Matcha and team stress that “[t]he single most important factor in preventing death in patients with diabetes is early recognition and surgical intervention, with tissue sampling for culture,” and highlight the need for education of healthcare providers who prescribe SGLT2 inhibitors.
They note that six patients in their study had more than one healthcare provider contact before they received a Fournier gangrene diagnosis, suggesting that the provider had initially failed to recognize the true problem.
“Systemic symptoms, such as fatigue, fever, and malaise, may be variable and nonspecific,” the researchers observe.
They say: “Pain that seems out of proportion to findings on physical examination is a strong clinical indicator of necrotizing fasciitis and may be the most important diagnostic clue”, and urge a “high index of suspicion” for the condition in patients using SGLT2 inhibitors.
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