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Kidney Week

Abstract: PO1010

Effect of Dapagliflozin on Risk for Fast Decline in eGFR: Analysis from DECLARE-TIMI 58 Trial

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Mosenzon, Ofri, Hadassah Medical Center, Jerusalem, Jerusalem, Israel
  • Wiviott, Stephen, Brigham & Women’s Hospital, Boston, Massachusetts, United States
  • L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
  • Dwyer, Jamie P., Vanderbilt University Medical Center, Nashville, TN, USA, Nashville, Tennessee, United States
  • Cahn, Avivit, Hadassah Medical Center, Jerusalem, Jerusalem, Israel
  • Goodrich, Erica L., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Rozenberg, Aliza, Hadassah Medical Center, Jerusalem, Jerusalem, Israel
  • Yanuv, Ilan, Hadassah Medical Center, Jerusalem, Jerusalem, Israel
  • Wilding, John Ph, Department of Cardiovascular and Metabolic Medicine, University of Liverpool, UK, Liverpool, United Kingdom
  • Leiter, Lawrence A., St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada
  • Bhatt, Deepak L., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Mcguire, Darren K., University of Texas Southwestern Medical Center, Dalas, Texas, United States
  • Ma, Ronald C., Dept of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong
  • Tankova, Tsvetalina, Department of Endocrinology, Medical University, Sofia, Bulgaria, Sofia, Bulgaria
  • Fredriksson, Martin, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
  • Gause-Nilsson, Ingrid A M I, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
  • Langkilde, Anna Maria, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
  • Sabatine, Marc S., Brigham & Women’s Hospital, Boston, Massachusetts, United States
  • Raz, Itamar, Hadassah Medical Center, Jerusalem, Jerusalem, Israel
Background

SGLT2 inhibitors may lead to short term decrease in eGFR with later stabilization and long-term reduction in risk for end stage kidney disease. Fast decline (FD) in eGFR can be defined as reduction of ≥3 ml/min/1.73m2/year and is associated with poor long-term renal prognosis. In this post hoc analysis we studied the effect of dapagliflozin (dapa) on risk for FD in the DECLARE-TIMI 58 trial.

Methods

In DECLARE-TIMI 58, 17,160 patients with T2D and established or increased risk for CVD, with mean baseline eGFR of 85.2 ml/min/1.73m2, were randomized to dapa vs. placebo and followed for median of 4.2 years. The risk for FD was compared between treatment arms.

Results

In the time frame of 0.5 years (after stabilization) to 4 years, the proportion of patients with FD was reduced with dapa vs. placebo (26.8% vs. 37.1%, respectively, p<0.0001) and in all subgroups assessed (Figure). The mean (SD) reduction in eGFR per year was 6.3 (3.7) vs. 0.0 (2.5) ml/min/1.73m2/year in FD (N=4,788) vs. non-FD (N=10,224) patients. In patients that had FD, mean (SD) reduction in eGFR was -5.9 (3.2) vs. -6.6 (4.1) ml/min/1.73m2/year in dapa vs. placebo arm, while in patients that did not have fast decline it was 0.2 (2.5) vs. -0.2(2.5) ml/min/1.73m2/year, respectively. The proportion of patients with FD during entire study period (i.e. 0-4 years) was also reduced with dapa vs. placebo (33.6% vs. 37.0%, respectively, p<0.0001).

Conclusion

Dapa reduced the risk for FD in eGFR in a broad population of patients with T2D and relatively preserved renal function, irrespective of patients’ baseline characteristics.

Funding

  • Commercial Support