RT Journal Article
SR Electronic
T1 Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering
JF BMJ Open Diabetes Research & Care
JO BMJ Open Diab Res Care
FD American Diabetes Association
SP e003270
DO 10.1136/bmjdrc-2022-003270
VO 11
IS 3
A1 David M Charytan
A1 Kenneth W Mahaffey
A1 Meg J Jardine
A1 Christopher P Cannon
A1 Bruce Neal
A1 Hiddo J Lambers Heerspink
A1 Rajiv Agarwal
A1 George L Bakris
A1 Dick de Zeeuw
A1 Adeera Levin
A1 Carol Pollock
A1 Hong Zhang
A1 Bernard Zinman
A1 Norman Rosenthal
A1 Vlado Perkovic
A1 Gian Luca Di Tanna
A1 Jie Yu
A1 Kris Rogers
A1 Clare Arnott
A1 David C Wheeler
YR 2023
UL http://drc.bmj.com/content/11/3/e003270.abstract
AB Introduction Relationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain.Research design and methods We analyzed 4395 individuals with prebaseline and postbaseline hemoglobin A1c (HbA1c) randomized to canagliflozin (n=2193) or placebo (n=2202) in The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects on HbA1c were assessed using mixed models. Mediation of treatment effects by achieved glycemic control was analyzed using proportional hazards regression with and without adjustment for achieved HbA1c. End points included combined kidney or cardiovascular death, end-stage kidney disease or doubling of serum creatinine (primary trial outcome), and individual end point components.Results HbA1c lowering was modified by baseline estimated glomerular filtration rate (eGFR). For baseline eGFR 60–90, 45–59, and 30–44 mL/min/1.73 m2, overall HbA1c (canagliflozin vs placebo) decreased by −0.24%, −0.14%, and −0.08% respectively and likelihood of >0.5% decrease in HbA1c decreased with ORs of 1.47 (95% CI 1.27 to 1.67), 1.12 (0.94 to 1.33) and 0.99 (0.83 to 1.18), respectively. Adjustment for postbaseline HbA1c marginally attenuated canagliflozin effects on primary and kidney composite outcomes: unadjusted HR 0.67 (95% CI 0.57 to 0.80) and 0.66 (95% CI 0.53 to 0.81); adjusted for week 13 HbA1c, HR 0.71 (95% CI 0.060 to 0.84) and 0.68 (95% CI 0.55 to 0.83). Results adjusted for time-varying HbA1c or HbA1c as a cubic spline were similar and consistent with preserved clinical benefits across a range of excellent and poor glycemic control.Conclusions The glycemic effects of canagliflozin are attenuated at lower eGFR but effects on kidney and cardiac end points are preserved. Non-glycemic effects may be primarily responsible for the kidney and cardioprotective benefits of canagliflozin.22Data may be obtained from a third party and are not publicly available.