EMPA-KIDNEY Post-Trial Findings

The EMPA-KIDNEY trial assessed the effects of treatment with empagliflozin on patients with CKD at risk for disease progression. During an oral presentation at ASN Kidney Week 2024, William G. Herrington, MBBS, MD, and colleagues described findings from an additional two years of post-trial follow-up (PTFU). The session was titled Long-Term Effects of Empagliflozin in CKD.

The study included patients with eGFR of 20-44 or eGFR 45-89 and urine albumin-to-creatinine ratio of ≥200 mg/g. Participants were randomized to empagliflozin or placebo and received treatment for a median of two years. After the study period, participants were studied off treatment, and local physicians could initiate an open-label SGLT2 inhibitor (maintaining blinding to the original allocation).

The primary composite outcome was progression of kidney disease or cardiovascular death for the full follow-up period (combination of the within-trial and PTFU periods). Of 6,609 randomized participants, 4,895 were included in PTFU and followed for a median of two years. SGLT2 inhibitor use was similar between the empagliflozin (43%) and placebo (40%) groups during the PTFU period.

In the empagliflozin group, a primary outcome occurred in 865 of 3,304 (26.2%) patients, and in the placebo group, a primary outcome occurred in 1,001 of 3,305 (30.3%) patients over the entire follow-up period (HR, 0.79; 95% CI, 0.72-0.87). Relative effects on the primary outcome did not significantly differ across key subgroups, such as diabetes, eGFR, and UACR. Post-trial, there was a 13% (HR, 0.87; 95% CI, 0.76-0.99) reduction in risk of the primary outcome, meaning the absolute differences in the primary outcome were 57 (standard error [SE] 14) per 1,000 at the end of the within-trial period and 45 (SE 14) at the end of PTFU.

Assignment to the empagliflozin treatment decreased the risk of kidney disease progression (23.5% vs 27.1%), the composite of death or end-stage renal disease (16.9% vs 19.6%), and cardiovascular death (3.8% vs 4.9%).

In conclusion, the post-trial follow-up of EMPA-KIDNEY provides a more complete measurement of the total effects of two years of empagliflozin. Although the drug provided benefits for cardiorenal outcomes for a period after discontinuation, the post-trial benefit was smaller than during treatment and seemed to be temporary. “To maximize the cardiorenal clinical benefits of SGLT2 inhibitors therefore requires long-term treatment of patients with CKD,” the researchers concluded.

Source: Herrington WG, Staplin N, Agrawal N, Haynes R. Long-term effects of empagliflozin in CKD. FR-OR103. Abstract of an oral presentation at the American Society of Nephrology Kidney Week 2024; October 25, 2024; San Diego, California. Commercial support was provided by Boehringer Ingelheim.