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Can Empagliflozin Slow Progression of Kidney Disease?

N Engl J Med; ePub 2016 Jun 14; Wanner, Inzucchi, et al

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When added to standard care, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events compared to placebo in patients with type 2 diabetes at high cardiovascular risk. This according to a randomized study which assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body surface area to receive either empagliflozin (10 mg or 20 mg) or placebo once daily. Researchers found:

• Incident or worsening nephropathy occurred in 525 of 4,124 patients (12.7%) in the empagliflozin group compared to 388 of 2,061 (18.8%) in the placebo group.

• Doubling of the serum creatinine level occurred in 70 of 4,645 patients (1.5%) in the empagliflozin group and in 60 of 2,323 (2.6%) in the placebo group; a significant relative risk reduction of 44%.

• Renal-replacement therapy was initiated in 13 of 4,867 patients (0.3%) in the empagliflozin group and in 14 of 2,333 patients (0.6%) in the placebo group; a 55% lower relative risk in the empagliflozin group.

• There was no significant between-group difference in the rate of incident albuminuria.

Citation: Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. [Published online ahead of print June 14, 2016]. N Engl J Med. doi:10.1056/NEJMoa1515920.

Commentary: This past fall the EMPA-REG study, comparing standard of care plus empagliflozin vs placebo in patients with diabetes and established CV disease, reported a positive effect of empagliflozin on macrovascular outcome and total mortality.1 Now further analysis of the data reports a positive effect on microvascular disease as well, specifically progression of diabetic nephropathy. It is important to note that this study was not primarily a test of blood glucose control, because both the empaglifozin and the placebo groups were randomized to drug plus the standard of care. Also important is that this improvement in renal outcomes occurred on top of over 80% of patients already receiving ACE inhibitors or ARBs at baseline, which is the current optimal intervention to slow progression of diabetic nephropathy. Now that we have two new medications, empagliflozin and liraglutide, that have shown important beneficial effects on hard outcomes when tested in very different populations of patients with type 2 diabetes, the challenging questions we will face are whether the effects are specific to these drugs or whether the effects are representative to these classes of medications, and then which medications to use in which groups of patients to obtain optimal outcomes. —Neil Skolnik, MD

1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-28. doi:10.1056/NEJMoa1504720.

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