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Abstract: FR-PO223

Renoprotective Effects of Canagliflozin in CREDENCE May Be Independent of Glucose-Lowering Mechanisms

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Charytan, David M., NYU School of Medicine and NYU Langone Medical Center, Bronx, New York, United States
  • Mahaffey, Kenneth W., Stanford University School of Medicine, Stanford, California, United States
  • Jardine, Meg J., The George Institute for Global Health, UNSW, Sydney, New South Wales, Australia
  • Agarwal, Rajiv, Indiana University School of Medicine and VA Medical Center, Indianapolis, Indiana, United States
  • Bull, Scott, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Chu, Pei-Ling, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • de Zeeuw, Dick, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Greene, Tom, University of Utah, Salt Lake City, Utah, United States
  • L Heerspink, Hiddo Jan, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Neal, Bruce, The George Institute for Global Health, UNSW, Sydney, Australia
  • Oh, Richard, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Pollock, Carol A., Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, St. Leonards, New South Wales, Australia
  • Zinman, Bernard, Lunenfeld-Tanenbaum Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  • Perkovic, Vlado, The George Institute for Global Health, UNSW, Sydney, New South Wales, Australia
  • Wheeler, David C., UCL Medical School, London, United Kingdom
Background

In the CREDENCE study, the SGLT2 inhibitor canagliflozin (CANA) improved renal and CV outcomes in patients with type 2 diabetes and CKD. Whether effects on CV and renal outcomes are explained by glucose lowering and how baseline kidney function modifies the glycemic effects of CANA are not completely understood.

Methods

Analyses were performed in the 4401 patients randomized to CANA (N=2202) or placebo (N=2199). ANCOVA was used to analyze differences in HbA1c at end of treatment. Cox models stratified by screening eGFR and including HbA1c and systolic BP as time-varying covariates were used to analyze time to event.

Results

Least squares (LS) mean (SE) changes in HbA1c during treatment were small: –0.38% (0.03) for CANA vs –0.25% (0.03) for PBO. LS mean differences between CANA and PBO in HbA1c from baseline to end of treatment overall and in subgroups by screening eGFR are shown (Figure). Despite no reduction in HbA1c in the lowest eGFR group, risk reduction for the primary composite endpoint of ESKD, doubling of serum creatinine, or renal or CV death did not differ by screening eGFR (HRs of 0.75, 0.52 and 0.82 for eGFR 30-<45, 45-<60, and 60-<90 ml/min/1.73m2, respectively; P-interaction=0.11). Risk reduction with CANA vs PBO after adjusting for running mean HbA1c (HR 0.74, 95% CI 0.63-0.88, P<0.001) was similar to the primary results (HR 0.70, 95% CI 0.59-0.82, P=0.00001). Running mean HbA1c was modestly associated with the primary outcome (HR per 1% change 1.13, 95% CI 1.06-1.21, P<0.001).

Conclusion

In patients with type 2 diabetes and CKD enrolled in CREDENCE, renoprotective benefits of CANA appear to be independent of HbA1c reduction and may be linked to non-glycemic properties of CANA.

Funding

  • Commercial Support