Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitors
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 thr...
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BMJ Publishing Group
2019-05-01
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| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/7/1/e000725.full |
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| author | Gian Paolo Fadini Mayur Sarangdhar Angelo Avogaro Emanuel Raschi Fabrizio De Ponti |
| author_facet | Gian Paolo Fadini Mayur Sarangdhar Angelo Avogaro Emanuel Raschi Fabrizio De Ponti |
| author_sort | Gian Paolo Fadini |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d14f86e4324e4e1baadcb104462c4323 |
| institution | Kabale University |
| issn | 2052-4897 |
| language | English |
| publishDate | 2019-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj-art-d14f86e4324e4e1baadcb104462c43232024-12-15T16:25:09ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972019-05-017110.1136/bmjdrc-2019-000725Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitorsGian Paolo Fadini0Mayur Sarangdhar1Angelo Avogaro2Emanuel Raschi3Fabrizio De Ponti4Department of Medicine, University of Padova, Padova, Italy2 Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USADepartment of Medicine, Division of Metabolic Diseases, University of Padova, Padua, Italyassociate professor of pharmacologyDepartment of Medical and Surgical Sciences, Pharmacology Unit, Alma Mater Studiorum, University of Bologna, Bologna, ItalyObjective 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.https://drc.bmj.com/content/7/1/e000725.full |
| spellingShingle | Gian Paolo Fadini Mayur Sarangdhar Angelo Avogaro Emanuel Raschi Fabrizio De Ponti Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitors BMJ Open Diabetes Research & Care |
| title | Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitors |
| title_full | Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitors |
| title_fullStr | Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitors |
| title_full_unstemmed | Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitors |
| title_short | Pharmacovigilance assessment of the association between Fournier’s gangrene and other severe genital adverse events with SGLT-2 inhibitors |
| title_sort | pharmacovigilance assessment of the association between fournier s gangrene and other severe genital adverse events with sglt 2 inhibitors |
| url | https://drc.bmj.com/content/7/1/e000725.full |
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