BACKGROUND: Limited knowledge exists regarding nephrotoxic risksassociated with the combination of sodium-glucose co-transporter-2 inhibitors(SGLT2i) and potentially nephrotoxic drugs. This study evaluates acute renalfailure (ARF) events linked to such combinations using data from the FDAAdverse Event Reporting System (FAERS). METHODS: Signal mining was performed by estimating reportingodds ratios (ROR), with validation through additive, multiplicative, andproportional reporting ratio (PRR) models. Logistic regression assessedmortality risk factors. RESULTS: Among 4,417,195 reports, 1,636 ARF cases wereassociated with SGLT2i combinations, primarily involving diuretics,lipid-lowering agents, and anticoagulants. The highest ARF risk was observedwith dapagliflozin-cefazolin [ROR adjusted (a) 59.63, 95% CI (9.96, 356.87)
ROR adjusted (b) 19.88, 95% CI (1.80, 219.21)
additive model [0.53]
multiplicative model [8.36]
PRR [8.53]]. Consistent associations were foundfor empagliflozin-allopurinol and canagliflozin-vancomycin. Among single drugs,12, including canagliflozin, met all four significance criteria for ARFsignals. Logistic regression revealed male patients had higher mortality risk(OR = 0.356, CONCLUSION: This study confirms prior evidence of ARF associatedwith the combined use of SGLT2i with diuretics or NSAIDs and identifies newrisks with proton pump inhibitors (PPIs), antigout medications, andanticoagulants. Male gender was a significant risk factor.