FDA Raises Kidney Warning with SGLT2 Inhibitors

The FDA has strengthened its existing warning about acute kidney injury in patients with type 2 diabetes taking the sodium-glucose cotransporter-2 (SGLT2) inhibitors canagliflozin and dapagliflozin.¹

The strengthening is in response to 101 reported instances of acute kidney injury occurring from March 2013 to October 2015, some of which required hospitalization and dialysis.
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“Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin. These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and nonsteroidal anti-inflammatory drugs,” the FDA wrote.

The FDA stresses the need to assess kidney function before starting either of these medications and periodically after beginning them.

The warning comes the same day that a study published in the New England Journal of Medicine reported that treatment with the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes at high cardiovascular risk was associated with slower progression of kidney disease and lower rates of renal events than placebo, when added to standard care.²

The researchers randomly assigned participants in the EMPA-REG OUTCOME trial to either empagliflozin or placebo. Incident or worsening nephropathy occurred in 525 of 4124 patients in the empagliflozin group and 388 of 2061 in the placebo group. Those in the empagliflozin group had a 55% lower relative risk of renal-replacement therapy and a 44% lower relative risk of doubling of serum creatinine levels than those in the placebo group.

“In patients with type 2 diabetes at high cardiovascular risk, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care,” the authors wrote.

—Michael Potts

References:

1. FDA. Canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR): drug safety communication - strengthened kidney warnings. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm506554.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery. Published June 14, 2016. Accessed June 15, 2016.
2. Wanner C, Inzucchi SE, Lackin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes [published online June 14, 2016]. N Engl J Med. doi:10.1056/NEJMoa1515920.