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

https://doi.org/10.1016/j.numecd.2017.10.011Get rights and content

Highlights

  • SGLT2-inhibitors are associated with acute renal failure in the FDA adverse event reporting system.

  • Reports of acute renal failure with SGLT2-inhibitors were more likely to report concomitant diuretics and/or ACE-inhibitors.

  • Plausible biological mechanisms have been proposed for these findings.

  • The link between SGLT2-inhibitors and acute renal failure persisted when controlling for diabetes and the FDA warning.

  • SGLT2-inhibitors differed from one another in the strength of their link to acute renal failure.

Abstract

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.

Section snippets

Background

Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have been approved in recent years for use in the treatment of type II diabetes mellitus (T2DM). Currently approved agents include canagliflozin, dapagliflozin, and empagliflozin. These agents have all proven effective treating T2DM in terms of HbA1c reduction, as well as additionally beneficial in terms of blood pressure reduction, weight loss, and improved lipid profile [1]. The large randomized control trial EMPA-REG demonstrated that

Methods

We analyzed adverse event cases submitted to FAERS between January 2013 and September 2016. FAERS is a database that contains information on adverse event reports submitted to FDA. The database is designed to support the FDA's post-marketing safety surveillance program for medication. Reports of adverse events are submitted by healthcare professionals (such as physicians, pharmacists, nurses and others), consumers (such as patients, family members, lawyers and others), and drug manufacturers

Results

During the period evaluated, 3,832,015 unique adverse event cases were reported in FAERS. Of these, 18,915 reports involved the use of SGLT2-inhibitors. Individuals reported with SGLT2-inhibitor associated adverse events were on average 58 years of age, and weighed 95 kg. SGLT2-inhibitors were reportedly associated with ARF in 1224 cases (6.5%), and were judged to be the “primary” or “secondary” cause of the adverse event in almost all cases (96.8%). Many of the cases reporting SGLT2-inhibitor

Discussion

The results of this study show that in the FDA adverse events database, SGLT2-inhibitors are associated with increased odds of reporting of acute renal failure. The strength of this association (ROR 2.88, 95% CI 2.71–3.05, p < 0.001) met widely accepted and validated criteria indicating a likely signal between these medications and acute renal failure, and the outcome of a large proportion of cases was deemed serious or led to new or prolonged hospitalization. The association between

Acknowledgments

No financial support was received for the conduct of the research and/or preparation of the article, and the authors have no conflict of interest to disclose.

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