Canagliflozin and Risk of Skin and Soft Tissue Infections in People with Diabetes Mellitus and Kidney Disease in the CREDENCE Trial
Year: 2020
Type: article
Abstract: 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 intentionto-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cases of necrotising fasciitis were in patients assigned to canagliflozin and the participants recovered after drug was withdrawn. Conclusions: 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 - Janssen sponsored the CREDENCE trial but did not sponsor this post-hoc analysis
Authors: Amy Kang, Brendan Smyth, Brendon L. Neuen, Hiddo J. L Heerspink, Gian Luca Di Tanna, Bruce Neal, Hong Zhang, Carinna Hockham, Rajiv Agarwal, George L. Bakris, David M. Charytan, Dick de Zeeuw, Tom Greene, Adeera Levin, Carol A. Pollock, David C. Wheeler, Bernard Zinman, Kenneth W. Mahaffey, Vlado Perkovic, Meg J. Jardine
Institutions: UNSW Sydney, The George Institute for Global Health, University of Groningen, Peking University First Hospital, Indiana University School of Medicine, University of Chicago, NYU Langone Health, University of Utah, University of Utah Health Care, University of British Columbia, The University of Sydney, University College London, Lunenfeld-Tanenbaum Research Institute, Stanford University
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4396997482