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Abstract: PO1000

Effects of Canagliflozin on Cardiovascular, Renal, and Safety Outcomes by Baseline Loop Diuretic Use: Data from the CREDENCE Trial

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Levin, Adeera, Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
  • Neuen, Brendon Lange, The George Institute for Global Health, Sydney, New South Wales, Australia
  • Mahaffey, Kenneth W., Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
  • Cannon, Christopher P., Cardiovasular Division, Brigham & Women’s Hospital and Baim Institute for Clinical Research, Boston, Massachusetts, United States
  • Jardine, Meg J., The George Institute for Global Health, Sydney, New South Wales, Australia
  • L Heerspink, Hiddo Jan, Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Neal, Bruce, The George Institute for Global Health, Sydney, Australia
  • Arnott, Clare Gabrielle, Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
  • Zhou, Zien, The George Institute for Global Health, Sydney, Australia
  • Charytan, David M., Nephrology Division, NYU School of Medicine and NYU Langone Medical Center, New York, New York, United States
  • Agarwal, Rajiv, Indiana University School of Medicine and VA Medical Center, Indianapolis, Indiana, United States
  • Bakris, George L., Department of Medicine, University of Chicago Medicine, Chicago, Illinois, United States
  • de Zeeuw, Dick, Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Greene, Tom, Division of Biostatistics, Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, United States
  • Wheeler, David C., Department of Renal Medicine, UCL Medical School, London, United Kingdom
  • Rosenthal, Norm, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • 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, Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
  • Pollock, Carol A., Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia
Background

Canagliflozin (CANA) reduces the risk of cardiovascular (CV) events and kidney failure in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Inherent in its mechanism of action is enhanced natriuresis and osmotic diuresis. It is unclear if the efficacy or safety of CANA is modified by concomitant diuretic use.

Methods

CREDENCE randomized participants with T2DM and CKD to CANA or matching placebo. The primary outcome was a composite of end-stage kidney disease, doubling of serum creatinine, CV or renal death. We estimated effects on key efficacy and safety outcomes by baseline use of loop diuretics.

Results

Of 4401 CREDENCE participants, 955 (21.7%) received loop diuretics at baseline. These participants were older (mean age 63.5 vs 62.7 y; P=0.01), with a longer diabetes duration (17.0 vs 15.5 y), lower eGFR (49.7 vs 58.0 mL/min/1.73m2), and were more like to have a history of heart failure (27.6 vs 11.3%; all P<0.0001). Unadjusted event rates were higher in those using loop diuretics (Figure). Effects of CANA on the primary outcome and other CV and renal outcomes were consistent irrespective of loop diuretic use. The risk of renal-related adverse events, acute kidney injury, and volume depletion was not elevated by loop diuretic use (data not shown; all Pinteraction>0.05).

Conclusion

CANA reduces the risk of CV and renal outcomes in people with T2DM and CKD irrespective of baseline use of loop diuretics, without additional adverse effects.

Funding

  • Commercial Support