Amputation and gangrene associated with SGLT2 inhibitors: pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) database.

BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed to diabetic patients for their cardiorenal benefits. However, concerns over adverse events—specifically amputation risk and gangrene—have risen in recent years. This study aimed to describe the frequency and severity of these events in relation to SGLT2 inhibitor use, using the U.S. FDA Adverse Event Reporting System (FAERS). METHODS: OpenVigil 2.1 was used to extract safety reports submitted to FAERS from 2003 Q4 to 2024 Q4. Amputation and gangrene events linked to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) were identified and compared to other drugs. Reporting odds ratios (RORs) were calculated. RESULTS: A total of 3,540 adverse event reports were identified: 2,128 for canagliflozin, 361 for dapagliflozin, 1,049 for empagliflozin, and 2 for ertugliflozin. Canagliflozin was strongly associated with toe amputation (ROR = 635.6; 95%CI: 566.7–712.1), foot amputation (ROR = 201.8; 95%CI: 174.3–233.7), and Fournier’s gangrene (ROR = 117.5; 95%CI: 100.0–138.0). Empagliflozin was linked with Fournier’s gangrene (ROR = 565.2; 95%CI: 525.3–608.2) and toe amputation (ROR = 21.2; 95%CI: 17.6–25.6). Dapagliflozin showed weaker signals; ertugliflozin had minimal data. CONCLUSION: Toe amputation and Fournier’s gangrene were most reported with canagliflozin and empagliflozin, reinforcing prior safety concerns and the need for monitoring.