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Kidney Week

Abstract: FR-OR103

Long-Term Effects of Empagliflozin in CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Herrington, William G., University of Oxford, Oxford, Oxfordshire, United Kingdom
  • Staplin, Natalie, University of Oxford, Oxford, Oxfordshire, United Kingdom
  • Agrawal, Nikita, University of Oxford, Oxford, Oxfordshire, United Kingdom
  • Haynes, Richard, University of Oxford, Oxford, Oxfordshire, United Kingdom

Group or Team Name

  • EMPA-KIDNEY Collaborative Group.
Background

We observed the cardiorenal effects of ~2 years of empagliflozin within EMPA-KIDNEY for an additional ~2 years of post-trial follow-up (PTFU).

Methods

Patients with an eGFR 20-<45; or 45-<90 and urine ACR of ≥200 mg/g were randomized to empagliflozin versus placebo and provided with allocated treatment for a median of 2 years. Post-trial, participants were then prospectively observed off study treatment. Local doctors were free to commence an open-label SGLT2 inhbitor (blinding to original 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, 4895 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 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% (0.87, 0.76-0.99) reduction in risk of the primary outcome post-trial (Figure). This meant the absolute differences in the primary outcome were 57 (SE14) 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%), the composite of death or end-stage kidney disease (16.9% vs 19.6%), and 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 a period 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.

Funding

  • Commercial Support – Boehringer Ingelheim