Kidney Week

Abstract: TH-PO1204

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

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

• Jardine, Meg J., The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Meg J. Jardine,

• Oshima, Megumi, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Megumi Oshima,

• Mahaffey, Kenneth W., Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States

Kenneth W. Mahaffey,

• Agarwal, Rajiv, Indiana University School of Medicine and VA Medical Center, Indianapolis, Indiana, United States

Rajiv Agarwal,

• Baldassarre, James S., Janssen Research & Development, LLC, Raritan, New Jersey, United States

James S. Baldassarre,

• Bakris, George L., Department of Medicine, University of Chicago Medicine, Chicago, Illinois, United States

George L. Bakris,

• Cannon, Christopher P., Cardiovascular Division, Brigham & Women’s Hospital and Baim Institute for Clinical Research, Boston, Massachusetts, United States

Christopher P. Cannon,

• Capuano, George, Janssen Research & Development, LLC, Raritan, New Jersey, United States

George Capuano,

• Charytan, David M., Nephrology Division, NYU School of Medicine and NYU Langone Medical Center, Bronx, New York, United States

David M. Charytan,

• de Zeeuw, Dick, Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Dick de Zeeuw,

• Edwards, Robert, Janssen Research & Development, LLC, Raritan, New Jersey, United States

Robert Edwards,

• Greene, Tom, Division of Biostatistics, Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, United States

Tom Greene,

• L Heerspink, Hiddo Jan, The George Institute for Global Health, UNSW Sydney, Newtown, Australia

Hiddo Jan L Heerspink,

• Levin, Adeera, Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada

Adeera Levin,

• Neal, Bruce, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Bruce Neal,

• Pollock, Carol A., Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia

Carol A. Pollock,

• Wheeler, David C., Department of Renal Medicine, UCL Medical School, London, LoNDON, United Kingdom

David C. Wheeler,

• Zhang, Hong, Renal Division of Peking University First Hospital, Beijing, China

Hong Zhang,

• Zinman, Bernard, Lunenfeld-Tanenbaum Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

Bernard Zinman,

• Perkovic, Vlado, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Vlado Perkovic,

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 – Janssen Research & Development, LLC