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Canagliflozin Reduces Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial

Heerspink, HJL; Oshima, M; Zhang, H; Li, J; Agarwal, R; Capuano, G; Charytan, DM; ... Jardine, MJ; + view all (2021) Canagliflozin Reduces Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial. American Journal of Kidney Diseases 10.1053/j.ajkd.2021.05.005. (In press). Green open access

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Abstract

RATIONALE AND OBJECTIVE: Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs). STUDY DESIGN: A randomized, double-blind, placebo-controlled, multicenter, international trial. SETTING AND PARTICIPANTS: 4,401 trial participants with T2DM, CKD, and urinary albumin:creatinine ratio >300-5000mg/g. INTERVENTIONS: Participants were randomly assigned to receive canagliflozin 100mg/day or placebo. OUTCOMES: Rates of kidney-related AEs were analyzed using an on-treatment approach, overall and by screening estimated glomerular filtration rate (eGFR) strata (30-<45, 45-<60, and 60-<90 mL/min/1.73m2). RESULTS: Canagliflozin was associated with a reduction in the overall incidence rate of kidney-related AEs (60.2 vs 84.0 per 1,000 patient-years; hazard ratio [HR]: 0.71 [95% confidence interval (CI): 0.61, 0.82]; P<0.001), with consistent results for serious kidney-related AEs (HR: 0.72 [95% CI: 0.51, 1.00]; P=0.05) and acute kidney injury (AKI; HR: 0.85 [95% CI: 0.64, 1.13]; P=0.3). The rates of kidney-related AEs were lower with canagliflozin relative to placebo across the 3 eGFR strata (HRs of 0.73, 0.60, and 0.81 for eGFR 30-<45, 45-<60, and 60-<90 mL/min/1.73m2, respectively; P-interaction=0.3), with similar results for AKI (P-interaction=0.9). Full recovery of kidney function within 30 days after an AKI event occurred more frequently with canagliflozin versus placebo (53.1% vs 35.4%; odds ratio: 2.2 [95% CI: 1.0, 4.7]; P=0.04). LIMITATIONS: Kidney-related AEs including AKI were investigator-reported and collected without central adjudication. Biomarkers of AKI and structural tubular damage were not measured and creatinine data after an AKI event were not available for all participants. CONCLUSION: Canagliflozin compared to placebo was associated with a reduced incidence of serious and non-serious kidney-related AEs in patients with T2DM and CKD. These results highlight the safety of canagliflozin with regard to adverse kidney disease events.

Type: Article
Title: Canagliflozin Reduces Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1053/j.ajkd.2021.05.005
Publisher version: https://doi.org/10.1053/j.ajkd.2021.05.005
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Canagliflozin, SGLT2 inhibitor, drug safety, renal-related adverse events
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10129422
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