Fournier's gangrene and sodium–glucose cotransporter 2 inhibitors: Is there a causal association?

Real-world evidence on sodium-glucose cotransporter-2 inhibitor use and risk of Fournier’s gangrene

“…The DPP4i comparator reflects the clinical decision between prescribing two similar branded second-line antihyperglycemic medications, whereas the non-SGLT2i comparator group contains a more heterogeneous set of medications including first-line metformin and third-line insulin as well as generic medications. Our results in the DPP4i comparison, which we believe to be the most relevant active-comparator class of glucose-lowering drugs to SGLT2i, are also corroborated by a recent meta-analysis of randomized trials30 as well as a recent commentary,12 both of which addressed the topic of FG risk and concluded no increased risk for SGLT2i users.…”

“…We estimated propensity scores using multivariable logistic regression to control for measured confounding, with baseline covariates (patient demographics, comorbidities, risk factors for FG,5 6 9 10 12 medication use history, and baseline healthcare utilization) measured in the 12 months prior to index date. All propensity score analyses were performed separately for patients with index dates before versus after 1 October 2015, to account for possible billing changes in the ICD-9 versus ICD-10 eras.…”

“…A more recent review of the FAERS and case reports yielded similar conclusions based on 55 FG cases among patients receiving SGLT2i from 2013 to 2019, compared with 19 FG cases among patients receiving other antihyperglycemic medications from 1984 to 2019 11. However, the structure and quality of FAERS reporting precluded any ability to estimate comparative incidence or establish causality 12…”

Fournier's gangrene in patients with type 2 diabetes using second‐line antidiabetic medications

“…Further, an examination of reported rates of FG from the published literature suggests an underestimation of FG events among patients treated with other classes of antiglycaemic agents. 9 These epidemiological data on the occurrence of FG/NF in patients with type 2 diabetes and second-line treatment do not support the initial indication, generated from single case reports, of an association with SGLTi use. This is congruent with randomized trial findings, although the cumulative numbers of events are small.…”

“…Based on these findings, the authors noted a potential increased risk of FG among SGLT‐2i users; however, their findings were not considered causal because of multiple confounding factors, including an increase in the reporting of events as a result of growing awareness of the safety issues, an increase in the population with type 2 diabetes resulting in an increase in the associated complications, as well as confounding by indication because of higher prescribing rates of SGLT‐2i to patients with a higher risk of CVD. Further, an examination of reported rates of FG from the published literature suggests an underestimation of FG events among patients treated with other classes of antiglycaemic agents …”