Long-Term Effects of Empagliflozin in CKD

Introduction In the EMPA-KIDNEY trial, the sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin had positive cardiorenal effects in patients with chronic kidney disease who were at risk for disease progression. Post-trial follow-up (PTFU) was designed to assess how the effects of empagliflozin would evolve after the discontinuation of the trial drug. EMPA-KIDNEY observed the cardiorenal effects of approx. 2 years of empagliflozin and the PTFU for an additional approx. 2 years afterwards.

Methods Patients with an estimated glomerular filtration rate (eGFR) of 20 to<45; or 45 to<90; and a urine albumin creatinine ratio (ACR) of≥200 mg/g were randomized to empagliflozin versus placebo and provided with allocated treatment for a median of 2 year. Post-trial, participants were prospectively observed off study treatment. Local doctors were free to commence an open-label SGLT2 inhibitor while blinding to original treatment allocation was maintained. The primary composite outcome was kidney disease progression or CV death for the entire follow-up period (i.e. within-trial+PTFU periods combined).

Results Of 6609 randomized participants, 4891 (74%) entered PTFU and were followed for a median of 2 years. During the post-trial period, any SGLT2 inhibitor use was similar between groups (average use of empagliflozin 43% vs. placebo 40%). Over the entirety of follow-up, a primary outcome occurred in 865/3304 participants (26.2%) in the empagliflozin group and in 1001/3305 (30.3%) in the placebo group (HR=0.79, 95% CI 0.72-0.87). Relative effects on the primary outcome were similar across the key subgroups (by diabetes, eGFR & uACR). There was a 13% (HR=0.87, 95% CI 0.76-0.99) reduction in risk of the primary outcome post-trial. This meant the absolute difference (±SE) in the primary outcome were 57 (±14) per 1000 at the end of the within-trial period and still 45 (±14) at the end of PTFU. Allocation to empagliflozin reduced risk of kidney disease progression (23.5% vs. 27.1%), risk of composite of death or end-stage kidney disease (16.9% vs 19.6%), and risk of CV death (3.8% vs. 4.9%).

Conclusion EMPA-KIDNEY PTFU quantifies more completely the total effects of the short period of 2 years of empagliflozin. Study empagliflozin continued to exert benefit on cardiorenal outcomes for up to 12 months after its discontinuation. The post-trial benefit was smaller than the benefit when taking study treatment and appeared to be temporary. To maximize the cardiorenal clinical benefits of SGLT2 inhibitors therefore requires long-term treatment of patients with CKD.

Publikationsverlauf

Artikel online veröffentlicht:
28. Mai 2025