Kidney Week

Abstract: TH-PO1205

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

Session Information

• Late-Breaking Clinical Trials Posters
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• No subcategory defined

Authors

• Mosenzon, Ofri, Hadassah Hebrew University Hospital, Jerusalem, Israel

Ofri Mosenzon,

• L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink,

• Dwyer, Jamie P., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Jamie P. Dwyer,

• Cahn, Avivit, Hadassah Hebrew University Hospital, Jerusalem, Israel

Avivit Cahn,

• Goodrich, Erica L, TIMI Study Group, Boston, Massachusetts, United States

Erica L Goodrich,

• Murphy, Sabina A, TIMI Study Group, Boston, Massachusetts, United States

Sabina A Murphy,

• Rozenberg, Aliza, Hadassah Hebrew University Medical Center, Jerusalem, Israel

Aliza Rozenberg,

• Yanuv, Ilan, Hadassah Hebrew University Medical Center, Jerusalem, Israel

Ilan Yanuv,

• Zelniker, Thomas A, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

Thomas A Zelniker,

• Bhatt, Deepak L, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

Deepak L Bhatt,

• Leiter, Lawrence A., St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada

Lawrence A. Leiter,

• Mcguire, Darren K., UT Southwestern Medical Center at Dallas, Dallas, Texas, United States

Darren K. Mcguire,

• Wilding, John Ph, University of Liverpool, Liverpool, United Kingdom

John Ph Wilding,

• Gause-Nilsson, Ingrid A M I, AstraZeneca, Gothenburg, Sweden

Ingrid A M I Gause-Nilsson,

• Langkilde, Anna Maria, AstraZeneca, Mölndal, Sweden

Anna Maria Langkilde,

• Fredriksson, Martin, AstraZeneca, Mölndal, Sweden

Martin Fredriksson,

• Johansson, Peter A, AstraZeneca, Mölndal, Sweden

Peter A Johansson,

• Sabatine, Marc S., TIMI Study Group, Boston, Massachusetts, United States

Marc S. Sabatine,

• Wiviott, Stephen, TIMI Study Group/Brigham and Women's Hospital, Boston, Massachusetts, United States

Stephen Wiviott,

• Raz, Itamar, Hadassah Hebrew University Medical Center, Jerusalem, Israel

Itamar Raz,

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

Funding

• Commercial Support –