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Kidney Week

Abstract: TH-PO1205

Prevention of CKD with Dapagliflozin: Analysis of the DECLARE-TIMI 58 Trial

Session Information

Category: Diabetic Kidney Disease

Authors

  • Mosenzon, Ofri, Hadassah Hebrew University Hospital, Jerusalem, Israel
  • L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
  • Dwyer, Jamie P., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Cahn, Avivit, Hadassah Hebrew University Hospital, Jerusalem, Israel
  • Goodrich, Erica L, TIMI Study Group, Boston, Massachusetts, United States
  • Murphy, Sabina A, TIMI Study Group, Boston, Massachusetts, United States
  • Rozenberg, Aliza, Hadassah Hebrew University Medical Center, Jerusalem, Israel
  • Yanuv, Ilan, Hadassah Hebrew University Medical Center, Jerusalem, Israel
  • Zelniker, Thomas A, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • Bhatt, Deepak L, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • Leiter, Lawrence A., St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada
  • Mcguire, Darren K., UT Southwestern Medical Center at Dallas, Dallas, Texas, United States
  • Wilding, John Ph, University of Liverpool, Liverpool, United Kingdom
  • Gause-Nilsson, Ingrid A M I, AstraZeneca, Gothenburg, Sweden
  • Langkilde, Anna Maria, AstraZeneca, Mölndal, Sweden
  • Fredriksson, Martin, AstraZeneca, Mölndal, Sweden
  • Johansson, Peter A, AstraZeneca, Mölndal, Sweden
  • Sabatine, Marc S., TIMI Study Group, Boston, Massachusetts, United States
  • Wiviott, Stephen, TIMI Study Group/Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Raz, Itamar, Hadassah Hebrew University Medical Center, Jerusalem, Israel
Background

Patients with early stage kidney disease incur low rates of hard renal endpoints, limiting the ability to demonstrate drug efficacy in this population. Consequently, the regulatory agencies including Federal Drug Administration and European Medicines Agency now consider eGFR based endpoints as acceptable surrogates. In the DECLARE-TIMI-58 study, dapagliflozin showed robust reduction in cardiorenal and renal specific composite outcomes in the overall population.

Methods

17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo and followed for a median of 4.2 years. The baseline eGFR was 85.3 ml/min/1.73m2 and only 7% of patients had an eGFR <60 ml/min/1.73m2. We analyzed eGFR slopes from randomization to end of treatment with dapagliflozin vs. placebo.

Results

Dapagliflozin attenuated the eGFR decline overall in the trial and in subgroups based on eGFR, UACR, use of ACEi/ARB and diuretics (table). Fewer patients experienced an eGFR decline of 30%, 40% or 50% to eGFR<60 with dapagliflozin vs. placebo, HR (95% CI): 0.68 (0.58, 0.79); 0.54 (0.43, 0.67); 0.57 (0.40, 0.81) respectively, all p<0.002.

Conclusion

Dapagliflozin slowed the progression of renal disease across all subgroups of patients with type 2 diabetes, even in patients with normal kidney function and in patients with normo-albuminuria, highlighting its potential for primary prevention of chronic kidney disease.

Mean eGFR slopes per year from randomization to EOT by treatment arm
PopulationMean eGFR slope per year
Placebo arm

(ml/min/1.73 m2/year)
 Mean eGFR slope per year
Dapagliflozin arm

(ml/min/1.73 m2/year)
 Mean difference in eGFR slopes per year
Between Dapagliflozin and Placebo
 
 mean (SD)P- Valuemean (SD)P- Valuemean (SD)P- Value
Overall-2.44 (0.02)<.0001-1.78 (0.02)<.00010.66 (0.03)<.0001
eGFR >=90-2.58 (0.03)<.0001-1.99 (0.03)<.00010.59 (0.04)<.0001
eGFR >=60-<90-2.5 (0.04)<.0001-1.76 (0.04)<.00010.74 (0.05)<.0001
eGFR <60-1.34 (0.11)<.0001-0.48 (0.11)<.00010.86 (0.16)<.0001
UACR <30 mg/g-2.12 (0.03)<.0001-1.57 (0.03)<.00010.55 (0.04)<.0001
UACR >=30-<=300 mg/g-2.85 (0.05)<.0001-2.08 (0.05)<.00010.76 (0.08)<.0001
UACR >300 mg/g-4.93 (0.13)<.0001-3.02 (0.12)<.00011.90 (0.18)<.0001
ACEi/ARB at Baseline-2.51 (0.03)<.0001-1.81 (0.03)<.00010.70 (0.04)<.0001
No ACEi/ARB at Baseline-2.22 (0.06)<.0001-1.67 (0.05)<.00010.55 (0.08)<.0001
Diuretic use-2.55 (0.04)<.0001-1.91 (0.04)<.00010.64 (0.06)<.0001
No diuretic use-2.4 (0.03)<.0001-1.71 (0.03)<.00010.69 (0.04)<.0001

Funding

  • Commercial Support