Empagliflozin and Kidney Function Decline in Patients with Type 2 Diabetes: A Slope Analysis from the EMPA-REG OUTCOME Trial

• Published in: Journal of the American Society of Nephrology Vol. 29; no. 11; pp. 2755 - 2769
• Main Authors: Wanner, Christoph, Heerspink, Hiddo J.L., Zinman, Bernard, Inzucchi, Silvio E., Koitka-Weber, Audrey, Mattheus, Michaela, Hantel, Stefan, Woerle, Hans-Juergen, Broedl, Uli C., von Eynatten, Maximilian, Groop, Per-Henrik
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.11.2018
• Subjects: Clinical Research; randomized controlled trials; chronic kidney disease; diabetes mellitus
• ISSN: 1046-6673; 1533-3450; 1533-3450
• DOI: 10.1681/ASN.2018010103

Empagliflozin slowed the progression of CKD in patients with type 2 diabetes and cardiovascular disease in the EMPA-REG OUTCOME Trial. In a prespecified statistical approach, we assessed treatment differences in kidney function by analyzing slopes of eGFR changes. Participants ( =7020) were randomized (1:1:1) to empagliflozin 10 mg/d, empagliflozin 25 mg/d, or placebo added to standard of care. We calculated eGFR slopes using random-intercept/random-coefficient models for prespecified study periods: treatment initiation (baseline to week 4), chronic maintenance treatment (week 4 to last value on treatment), and post-treatment (last value on treatment to follow-up). Compared with placebo, empagliflozin was associated with uniform shifts in individual eGFR slopes across all periods. On treatment initiation, adjusted mean slope (eGFR change per week, ml/min per 1.73 m ) decreased with empagliflozin (-0.77; 95% confidence interval, -0.83 to -0.71; placebo: 0.01; 95% confidence interval, -0.08 to 0.10; <0.001). However, annual mean slope (ml/min per 1.73 m per year) did not decline with empagliflozin during chronic treatment (empagliflozin: 0.23; 95% confidence interval, 0.05 to 0.40; placebo: -1.46; 95% confidence interval, -1.74 to -1.17; <0.001). After drug cessation, the adjusted mean eGFR slope (ml/min per 1.73 m per week) increased and mean eGFR returned toward baseline level only in the empagliflozin group (0.56; 95% confidence interval, 0.49 to 0.62; placebo -0.02; 95% confidence interval, -0.12 to 0.08; <0.001). Results were consistent across patient subgroups at higher CKD risk. The hemodynamic effects of empagliflozin, associated with reduction in intraglomerular pressure, may contribute to long-term preservation of kidney function.