A Case Series and Literature Review of SGLT2 Inhibitors and Fournier s Gangrene: an Overlooked Rare Interaction

Special Article: Minimally Invasive Surgery

Austin J Surg. 2023; 10(5): 1315.

A Case Series and Literature Review of SGLT2 Inhibitors and Fournier’s Gangrene: an Overlooked Rare Interaction

Ahmad Saadya MBBCh, MRCS¹; Miss Eleni Hadjikyriacou, MBBCh, MRCS²

1Queen Victoria Hospital, East Grinstead, UK

2Morriston Hospital, United Kingdom

*Corresponding author: Ahmad Saadya Department of Plastic and reconstructive surgery, Queen Victoria Hospital, Holtye Rd, East Grinstead RH19 3DZ, UK Tel: +447846601739 Email: a.saadya@nhs.net

Received: September 25, 2023 Accepted: October 21, 2023 Published: October 28, 2023

Abstract

Introduction: Fournier’s Gangrene (FG) is a rare but life-threatening genital infection that can occur in vulnerable patients, especially diabetic patients. Literature evidence is suggesting that novel diabetic medication Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors can cause Fournier’s gangrene.

Patients and Methods: We report three cases of patients with Fournier’s gangrene we have treated who have been using the novel Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors for the treatment of type II diabetes mellitus and our experience treating them. We also inspect the current literature looking into the incidence of this rare event and the link to this class of medications.

We also have done a brief review of 24 articles including published case reports, pharmacovigilance studies, systematic reviews and meta-analysis, retrospective and cohort studies was done. Literature review showed an obvious link between SGLT2 inhibitors and FG.

Conclusion: The rising number of FG cases since the introduction Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors should be alarming to the prescribing physician and patients should be evaluated carefully for their risk factors for Fournier’s gangrene. Surgeons should suspect the incidence of Fournier’s gangrene in any patient presenting with signs of sepsis and signs of genital infection and using Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors. Patient education about the risk is needed to initiate prompt diagnosis and treatment. After life-saving measures like surgical debridement and antibiotics, the SGLT2 inhibitor agent should be discontinued and alternative therapy for glycaemic control should be provided.

Abbreviations: SGLT2: Sodium-glucose Cotransporter-2; FG: Fournier’s Gangrene; Reconstruction

Introduction

In 2018, the US Food and Drug Administration (FDA) issued a black box warning about multiple case reports of Fournier’s gangrene that were observed in patients using Sodium-Glucose cotransporter 2 (SGLT2) inhibitors. The UK Medicines and Healthcare products Regulatory Agency (MHRA) in 2019 has also issued a warning regarding the possible link between the use of Sodium-glucose cotransporter 2 (SGLT2) inhibitors and the developing of Fournier’s gangrene. Dapagliflozin and canagliflozin are Sodium-Glucose cotransporter 2 (SGLT2) inhibitors used in the treatment of type II diabetes mellitus. Fournier’s gangrene is a type of necrotizing fasciitis that happens in the urogenital area.

Materials/Patients

We report three cases of patients with Fournier’s gangrene we have treated who have been using the novel Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors for the treatment of type II diabetes mellitus and our experience treating them. We also inspect the current literature looking into the incidence of this rare event and the link to this class of medications.

We also have done a brief review of 24 articles including published case reports, pharmacovigilance studies, systematic reviews and meta-analysis, retrospective and cohort studies was done. Literature review showed an obvious link between SGLT2 inhibitors and FG.

Discussion

Despite being a rare condition, Fournier’s Gangrene (FG) remains one of the most dangerous life-threatening infections. Fournier’s Gangrene (FG) is a special type of necrotizing fasciitis infection that happens in the groin and perineal area. With high chances of mortality, prompt diagnosis and surgical intervention are crucial, and it is combined with different treatment modalities like antibiotics and multiple organ support to achieve good recovery. Fournier’s Gangrene (FG) susceptible population includes diabetic patients and immunosuppressed individuals with other risk factors like male gender, alcoholism, and hypertension.

Sodium-Gucose cotransporter 2 (SGLT2) inhibitors are orally administered antidiabetic drugs. They act by inhibiting the reabsorption of glucose from the urine by binding to SGLT2 in the proximal tubules of the kidney. This class of medications has been widely used in the past decade with impressive results. Studies showed a significant reduction in HBA1c, increased insulin sensitivity with a reduction of cardiac preload, and improving renal and hepatic functions. Sodium-Glucose cotransporter 2 (SGLT2) inhibitors also carry a notable multiple-risk profile that includes but not limited to diabetic ketoacidosis, urogenital infections, and acute kidney injury [1].

In 2018, the US Food and Drug Administration (FDA) issued a warning about multiple case reports of Fournier’s gangrene that were observed in patients using Sodium-Glucose cotransporter 2 (SGLT2) inhibitors [2]. The UK Medicines and Healthcare products Regulatory Agency (MHRA) in 2019 has also issued a warning regarding the possible link between the use of Sodium-glucose cotransporter 2 (SGLT2) inhibitors and the developing of Fournier’s gangrene [3].

Case Series

Case 1

A 61-year-old male patient presented with signs of septic shock to the emergency department. The patient’s medical history was significant for type II diabetes mellitus treated with Dapagliflozin and Metformin and hypertension treated with Amlodipine, Atenolol, Lisinopril, Doxazocin and Spironolactone and hypercholesteremia treated with atorvastatin and he was on a lifelong clopidogrel after having a cerebrovascular accident. The patient has been taking dapagliflozin for 11 months and has been diabetic for 10 years. On examination, patient had an abscess in the right groin, hemi-scrotum, and buttock with a wide area of necrotic tissue and foul-smelling discharge.

He was admitted for emergency surgery and debridement. The procedures included incision, drainage, and debridement of the right groin, hemi-scrotum, and buttock abscess with end colostomy, and he was transferred to intensive care unit post-operatively (Figure 1). The patient was treated with IV antibiotics (Meropenem and Clindamycin) and had a 2nd surgery 3 days later for a 2nd look and debridement and was subsequently moved to a ward care level 6 days after the 2nd look.