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.
Keywords
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Article info
Publication history
Published online: October 17, 2017
Accepted:
October 6,
2017
Received in revised form:
September 3,
2017
Received:
May 5,
2017
Handling Editor: Prof. A. GiaccariIdentification
Copyright
© 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
