Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: Analysis of the FDA adverse event report system database

Nutr Metab Cardiovasc Dis. 2017 Dec;27(12):1108-1113. doi: 10.1016/j.numecd.2017.10.011. Epub 2017 Oct 18.


Background and aims: Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have recently been approved for the treatment of type II diabetes mellitus (T2DM). It has been proposed that these agents could induce acute renal failure (ARF) under certain conditions. This study aimed to evaluate the association between SGLT2-inhibitors and ARF in the FDA adverse event report system (FAERS) database.

Methods and results: We analyzed adverse event cases submitted to FAERS between January 2013 and September 2016. ARF cases were identified using a structured medical query. Medications were identified using both brand and generic names. During the period evaluated, 18,915 reports (out of a total of 3,832,015 registered in FAERS) involved the use of SGLT2-inhibitors. SGLT2-inhibitors were reportedly associated with ARF in 1224 of these cases (6.4%), and were defined as the "primary" or "secondary" cause of the adverse event in 96.8% of these cases. The proportion of reports with ARF among reports with SGLT2 inhibitor was almost three-fold higher compared to reports without these drugs (ROR 2.88, 95% CI 2.71-3.05, p < 0.001). The proportion of ARF reports among cases with SGLT2-inhibitors was significantly greater than the proportion of ARF among cases with T2DM without SGLT2-inhibitors (ROR 1.68, 95% CI 1.57-1.8, p < 0.001). Among the SGLT2-inhibitors, canagliflozin was associated with a higher proportion of reports of renal failure (7.3%), compared to empagliflozin and dapagliflozin (4.7% and 4.8% respectively, p < 0.001).

Conclusion: SGLT2-inhibitors are associated with an increase in the proportion of reports of ARF compared to other medications. SGLT2-inhibitor agents may differ from one another in their respective risk for ARF.

Keywords: Adverse effects; Diabetes; Renal failure; SGLT2 inhibitors.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / diagnosis
  • Adverse Drug Reaction Reporting Systems*
  • Chi-Square Distribution
  • Databases, Factual
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Logistic Models
  • Odds Ratio
  • Patient Safety
  • Pharmacovigilance*
  • Risk Assessment
  • Risk Factors
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Time Factors
  • United States
  • United States Food and Drug Administration*


  • Hypoglycemic Agents
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors