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Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitors
  1. Gian Paolo Fadini1,
  2. Mayur Sarangdhar2,
  3. Fabrizio De Ponti3,
  4. Angelo Avogaro1,
  5. Emanuel Raschi3
  1. 1Department of Medicine, University of Padova, Padova, Italy
  2. 2Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
  3. 3Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
  1. Correspondence to Professor Gian Paolo Fadini; gianpaolofadini{at}hotmail.com

Abstract

Objective Sodium glucose cotransporter-2 inhibitors (SGLT2i) exert cardiorenal protection in people with diabetes. By inducing glycosuria, SGLT2i predispose to genital infections. In addition, rare occurrence of Fournier’s gangrene (FG) has been reported. We aimed to investigate such association through the U.S. Food and Drug Administration (FDA) adverse event (AE) reporting system (FAERS).

Research design and methods We mined the FAERS up to 2018q3 (before FDA warning about SGLT2i-associated FG) to retrieve reports including FG as an AE and SGLT2i as suspect or concomitant drugs, and calculated proportional reporting ratios (PRR).

Results We retrieved 47 cases of FG and 17 cases of other severe AEs of the genital area associated with SGLT2i. Patients with FG were ~10 years older than those with other severe genital AEs. Overall, 77% occurred in men. Three patients were concomitantly treated with systemic immunosuppressive drugs. Increased reporting frequency emerged for SGLT2i compared with other drugs, with a PRR ranging from 5 to 10. The disproportional reporting of FG with SGLT2i remained robust and consistently significant when restricting to the period when SGLT2i were available, to reports filed for glucose-lowering medications or for drugs with the diabetes indication, and after refining the definition of FG. FG was disproportionally associated with psoriasis and with the combination of immunosuppressants and SGLT2i.

Conclusions Although causality cannot be demonstrated, SGLT2i may predispose to FG and other severe genital AEs. Since the use of SGLT2i is expected to increase significantly, clinicians should be aware of these severe, although rare, AEs and their predisposing factors.

  • sodium glucose cotransporter
  • pharmacological therapy
  • type 2 diabetes
  • adverse drug reactions

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Footnotes

  • Contributors GPF: study design, data collection, analysis and interpretation, manuscript writing. MS: data collection and analysis, manuscript revision. FDP: data analysis and interpretation, manuscript revision. AA: study design, data interpretation, manuscript revision. ER: study design, data collection, analysis and interpretation, manuscript writing. All authors provided substantial contributions to conception and design, acquisition of data or analysis and interpretation of data, drafting the article or revising it critically for important intellectual content. All authors approved the final version to be published.

  • Funding The study was supported by institutional grants from the University of Padova and received no specific funding. The corresponding author had full access to all of the data and the final responsibility to submit for publication.

  • Competing interests GPF reports grants, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Boehringer-Ingelheim, personal fees from Mundipharma during the conduct of the study; grants, personal fees and non-financial support from Eli Lilly, personal fees and non-financial support from NovoNordisk, personal fees and non-financial support from Sanofi, non-financial support from Genzyme, personal fees and non-financial support from Abbott, personal fees and non-financial support from Novartis, personal fees from Merck Sharp & Dohme, outside the submitted work. AA reports grants, personal fees and non-financial support from AstraZeneca, personal fees from Boehringer-Ingelheim, personal fees from Janssen, during the conduct of the study; personal fees from Merck Sharp & Dome, personal fees and non-financial support from Novartis, personal fees from Sanofi, grants and personal fees from Mediolanum, personal fees from NovoNordisk, personal fees from Lilly, personal fees and non-financial support from Servier, personal fees from Takeda, outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information.

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