Empagliflozin Benefits on Kidney Disease Progression, Death Continue for 1 Year Post-Discontinuation

Will Herrington, MA, MBBS, MD, FRCP, FERA

Credit: Oxford University

Post-trial follow-up (PTFU) of the EMPA-KIDNEY trial has revealed that empagliflozin continues to benefit cardiorenal outcomes for a period of time after discontinuation in patients with chronic kidney disease (CKD).1

Data from the EMPA-KIDNEY PTFU were presented at The American Society of Nephrology (ASN) Kidney Week 2024, held October 23- 26 in San Diego, California, by Will Herrington, MA, MBBS, MD, FRCP, FERA, Professor of Trials and Epidemiology of Kidney Disease, Renal Studies Group, Nuffield Department of Population Health, and practicing Honorary Consultant Nephrologist, Oxford Kidney Unit, Oxford University.

“We weren't expecting to see such a substantial carryover effect. The carryover effect was not just for the primary outcomes, kidney function related outcomes, we could see carryover effects for hard clinical outcomes, by which I mean the composite of death or end stage kidney disease or end stage kidney disease considered in isolation. So, this carryover effect was having effects on hard clinical outcomes,” Herrington told HCPLive.

In EMPA-KIDNEY, participants with an eGFR between 20 and 45 or 45 and 90 and urine ACR of up to 200 mg/g were randomized to empagliflozin versus placebo and treated for a median of 2 years. Open-label SGLT2 inhibitors were allowed. The trial’s primary composite outcome was kidney disease progression or cardiovascular death, measured during the original trial and PTFU.

In this presentation, Herrington presented data from 4895 of 6609 randomized participants from EMPA-KIDNEY that entered the PTFU and were followed for a median of 2 years while off study treatment. SGLT2 inhibitor use was similar between patients that received empagliflozin (43%) and placebo (40%) during the PTFU. Kidney disease progression or cardiovascular death occurred in 865/3305 (26.2%) participants that received empagliflozin and 1001/3305 (30.3%) that received placebo over the entirety of follow-up (hazard ratio [HR], 0.79 [95% CI, 0.72-0.87]). Findings were similar across subgroups of diabetes, eGFR and urine albumin-creatinine ratio.

Post-trial, participants that received empagliflozin had a 13% reduction (HR, 0.87 [95% CI, 0.76-0.99]) in the risk of kidney disease progression or cardiovascular death. Overall, the absolute differences in this primary outcome were 57 (standard error [SE], 14) per 1000 at the end of main trial and still a significant 45 (SE, 14) per 1000 at the end of PTFU. Specifically, participants that received empagliflozin had a 23.5% risk of kidney disease progression, a 16.9% composite risk of end-stage kidney disease or death, and a 3.8% risk of cardiovascular death, compared to 27.1%, 19.6%, and 4.9% risks, respectively, in those that received placebo.

“The corollary of all of this means that the drug is safe. The drug works, it will continue to work for about a year after you stop taking it. But if you stop taking it for more than a year, then you lose all of the benefits. And of course, the effects post-trial are smaller than the effects when you take the drug. So really, we should be ensuring our patients stay on the drug at the at the full dose long term to ensure we maximize their benefits,” Herrington said.

REFERENCE

1. ^{Herrington WG, Staplin N, Agrawal R, Haynes R, Renal Studies Group. Long-Term Effects of Empagliflozin in CKD. Presented at: ASN Kidney Week 2024, October 13-26; San Diego, California.}
2. ^{The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117-127. doi:10.1056/NEJMoa2204233}