Kidney Week

Abstract: PO1005

Canagliflozin and Risk of Skin and Soft Tissue Infections in People with Diabetes Mellitus and Kidney Disease in the CREDENCE Trial

Session Information

• Diabetic Kidney Disease: Clinical - 2
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Kang, Amy, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Amy Kang,

• Smyth, Brendan, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Brendan Smyth,

• Neuen, Brendon Lange, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Brendon Lange Neuen,

• L Heerspink, Hiddo Jan, Rijksuniversiteit Groningen, Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink,

• Di Tanna, Gian Luca, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Gian Luca Di Tanna,

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

Bruce Neal,

• Zhang, Hong, Peking University First Hospital, Beijing, Beijing, China

Hong Zhang,

• Hockham, Carinna, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Carinna Hockham,

• Agarwal, Rajiv, Indiana University School of Medicine, Indianapolis, Indiana, United States

Rajiv Agarwal,

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

George L. Bakris,

• Charytan, David M., NYU Langone Health, New York, New York, United States

David M. Charytan,

• de Zeeuw, Dick, Rijksuniversiteit Groningen, Groningen, Groningen, Netherlands

Dick de Zeeuw,

• Greene, Tom, University of Utah Health, Salt Lake City, Utah, United States

Tom Greene,

• Levin, Adeera, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada

Adeera Levin,

• Pollock, Carol A., University of Sydney - Camperdown and Darlington Campus Burkitt-Ford Library, Sydney, New South Wales, Australia

Carol A. Pollock,

• Wheeler, David C., University College London, London, London, United Kingdom

David C. Wheeler,

• Zinman, Bernard, Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada

Bernard Zinman,

• Mahaffey, Kenneth W., Stanford University, Stanford, California, United States

Kenneth W. Mahaffey,

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

Vlado Perkovic,

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

Meg J. Jardine,

Background

The skin’s hypertonic microenvironment has a protective antimicrobial function that may be disrupted by sodium glucose cotransporter 2 inhibitors (SGLT2i). We aimed to describe skin and soft tissue infections (SSTI) in the CREDENCE trial and determine whether canagliflozin affects the risk of SSTIs.

Methods

We performed a post-hoc analysis of the CREDENCE trial that randomised people with type 2 diabetes and albuminuric stage 2 and 3 chronic kidney disease to either canagliflozin 100mg daily or placebo. Adverse events were assessed by two blinded authors following predetermined criteria for SSTI with discrepancies resolved by consensus. We analysed the risks of SSTIs in the on-treatment population as the more conservative approach, with sensitivity analyses conducted in the intention-to-treat population, for serious events only and for participant subgroups. Univariable time-to first-event regression models were assessed.

Results

Overall 373/4397 (8.5%) participants experienced 478 events comprising 252 bacterial skin infections (including 2 episodes of necrotising fasciitis), 94 fungal skin infections, 109 other skin infections and 23 soft tissue infections. Of these, 136/478 (28%) were serious.

Canagliflozin did not increase the risk of SSTI (HR 0.85 [95% Confidence Interval (CI) 0.69-1.04] p=0.11), with similar results in the intention-to-treat population (HR 0.88 [95% CI 0.73-1.07] p=0.20), in analyses confined to serious SSTI (HR 0.83 [95% CI 0.58-1.21] p=0.33) and participant subgroups (all p interaction≥0.10). Both cases of necrotising fasciitis were in patients assigned to canagliflozin and the participants recovered after drug was withdrawn.

Conclusion

Canagliflozin did not increase the risk of skin and soft tissue infections overall or in any subgroup, in CREDENCE trial participants with type 2 diabetes mellitus and albuminuric chronic kidney disease.

Funding

• Commercial Support –