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Effects of Canagliflozin in Patients with Baseline eGFR <30 ml/min per 1.73 m²: Subgroup Analysis of the Randomized CREDENCE Trial

Bakris, G; Oshima, M; Mahaffey, KW; Agarwal, R; Cannon, CP; Capuano, G; Charytan, DM; ... Perkovic, V; + view all (2020) Effects of Canagliflozin in Patients with Baseline eGFR <30 ml/min per 1.73 m²: Subgroup Analysis of the Randomized CREDENCE Trial. Clinical Journal of the American Society of Nephrology 10.2215/CJN.10140620. Green open access

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Abstract

BACKGROUND AND OBJECTIVES: The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial demonstrated that the sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin reduced the risk of kidney failure and cardiovascular events in participants with type 2 diabetes mellitus and CKD. Little is known about the use of SGLT2 inhibitors in patients with eGFR <30 ml/min per 1.73 m². The participants in the CREDENCE study had type 2 diabetes mellitus, a urinary albumin-creatinine ratio >300–5000 mg/g, and an eGFR of 30 to <90 ml/min per 1.73 m² at screening. This post hoc analysis evaluated participants with eGFR <30 ml/min per 1.73 m² at randomization. DESIGN, SETTING, PARTICIPATNS & MEASUREMENTS: Effects of eGFR slope through week 130 were analyzed using a piecewise, linear, mixed-effects model. Efficacy was analyzed in the intention-to-treat population, on the basis of Cox proportional hazard models, and safety was analyzed in the on-treatment population. At randomization (an average of 29 days after screening), 174 of 4401 (4%) participants had an eGFR <30 ml/min per 1.73 m² (mean [SD] eGFR, 26 [3] ml/min per 1.73 m²). RESULTS: From weeks 3 to 130, there was a 66% difference in the mean rate of eGFR decline with canagliflozin versus placebo (mean slopes, −1.30 versus −3.83 ml/min per 1.73 m² per year; difference, −2.54 ml/min per 1.73 m² per year; 95% confidence interval [CI], 0.90 to 4.17). Effects of canagliflozin on kidney, cardiovascular, and mortality outcomes were consistent for those with eGFR <30 and ≥30 ml/min per 1.73 m² (all P interaction >0.20). The estimate for kidney failure in participants with eGFR <30 ml/min per 1.73 m² (hazard ratio, 0.70; 95% CI, 0.54 to 0.91; P interaction=0.80). There was no imbalance in the rate of kidney-related adverse events or AKI associated with canagliflozin between participants with eGFR <30 and ≥30 ml/min per 1.73 m² (all P interaction >0.12). CONCLUSIONS: This post hoc analysis suggests canagliflozin slowed progression of kidney disease, without increasing AKI, even in participants with eGFR <30 ml/min per 1.73 m².

Type: Article
Title: Effects of Canagliflozin in Patients with Baseline eGFR <30 ml/min per 1.73 m²: Subgroup Analysis of the Randomized CREDENCE Trial
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.2215/CJN.10140620
Publisher version: https://doi.org/10.2215/CJN.10140620
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, chronic kidney disease, diabetes, diabetic nephropathy
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/10117112
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