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Kidney Week

Abstract: TH-PO1204

Impact of Canagliflozin (CANA) on eGFR Slope in People with Optimized Glucose Control: Randomized Analyses from CREDENCE

Session Information

Category: Diabetic Kidney Disease

Authors

  • Jardine, Meg J., The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia
  • Oshima, Megumi, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia
  • Mahaffey, Kenneth W., Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
  • Agarwal, Rajiv, Indiana University School of Medicine and VA Medical Center, Indianapolis, Indiana, United States
  • Baldassarre, James S., Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Bakris, George L., Department of Medicine, University of Chicago Medicine, Chicago, Illinois, United States
  • Cannon, Christopher P., Cardiovascular Division, Brigham & Women’s Hospital and Baim Institute for Clinical Research, Boston, Massachusetts, United States
  • Capuano, George, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Charytan, David M., Nephrology Division, NYU School of Medicine and NYU Langone Medical Center, Bronx, New York, United States
  • de Zeeuw, Dick, Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Edwards, Robert, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Greene, Tom, Division of Biostatistics, Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, United States
  • L Heerspink, Hiddo Jan, The George Institute for Global Health, UNSW Sydney, Newtown, Australia
  • Levin, Adeera, Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
  • Neal, Bruce, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia
  • Pollock, Carol A., Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
  • Wheeler, David C., Department of Renal Medicine, UCL Medical School, London, LoNDON, United Kingdom
  • Zhang, Hong, Renal Division of Peking University First Hospital, Beijing, China
  • 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, Newtown, New South Wales, Australia
Background

SGLT2 inhibitors were developed to lower glucose. Renal and cardiovascular (CV) protection from CANA in CREDENCE was seen in participants with type 2 diabetes overall, and in those with reduced eGFR in whom systemic glycemic effects are attenuated suggesting clinical benefits are not entirely mediated by glycemic improvements. We explored this by assessing the impact of CANA on eGFR slope in participants with HbA1c<7% vs those with HbA1c≥7%.

Methods

Relative and absolute effects of CANA on renal and CV outcomes were estimated using Cox proportional hazards regression. Effects of on-treatment eGFR slope were analyzed using a piecewise, 2-slope linear mixed effects model with a knot at week 3.

Results

At baseline, 650 (14.8%) participants had HbA1c<7% (mean 6.6%) and they had lower eGFR than the HbA1c≥7% cohort (53.5 vs 56.7 mL/min/1.73m2). CANA resulted in an acute drop in eGFR in those with HbA1c<7% (CANA vs placebo: 3.8±0.4 vs 0.5±0.4; Diff: 3.3 [95% CI: 2.1–4.5] mL/min/1.73m2) and HbA1c≥7% (3.3±0.2 vs 0.4±0.2; Diff: 2.9 [95% CI: 2.4–3.5] mL/min/1.73m2; Figure). CANA thereafter attenuated annualized eGFR decline in those with HbA1c<7% (2.3±0.4 vs 4.0±0.4; Diff: 1.8 [95% CI: 0.8–2.8] mL/min/1.73m2/year) and HbA1c≥7% (1.9±0.2 vs 4.9±0.2; Diff: 3.0 [95% CI: 2.5–3.4] mL/min/1.73m2/year). Primary and secondary outcomes were consistent in those with HbA1c<7% and ≥7%.

Conclusion

CANA appears to slow renal function loss in those with optimized HbA1c consistent with non-glucose mediated mechanisms of benefit.

Funding

  • Commercial Support