Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes According to Baseline HbA1c and Insulin Use: An Analysis From the FIDELIO-DKD Study
Peter Rossing, Ellen Burgess, Rajiv Agarwal, Stefan D. Anker, Gerasimos Filippatos, Bertram Pitt, Luís M. Ruilope, Pieter Gillard, Richard J. MacIsaac, Julio Wainstein, Amer Joseph, Meike Brinker, Lothar Roessig, Charlie Scott, George L. Bakris, FIDELIO-DKD Investigators, Augusto Vallejos, Richard J. MacIsaac, Guntram Schernthaner, Pieter Gillard, Maria Eugênia Fernandes Canziani, Theodora Temelkova‐Kurktschiev, Ellen Burgess, Sheldon W. Tobe, Fernando González, Zhi-Hong Liu, Andrés Ángelo, Cadena Bonfanti, Carlos Jaramillo, Martin Prázný, Peter Rossing, Jorma Strand, Michel Marre, Roland E. Schmieder, Christoph Wanner, Pantelis Sarafidis, Juliana C.N. Chan, László Rosivall, Joseph A. Eustace, Ehud Grossman, Yoram Yagil, Giuseppe Remuzzi, Daisuke Koya, Takashi Wada, Magdalena Madero Rovalo, Ron T. Gansevoort, Adriaan Kooy, Trine Finnes, Froilan De Leon, Janusz Gumprecht, Fernando Teixeira e Costa, Alexander Dreval, Anantharaman Vathsala, Aslam Amod, Sin Gon Kim, Byung‐Wan Lee, Julio Pascual Santos, Bengt-Olov Tengmark, Michel Burnier, Chien‐Te Lee, Sukit Yamwong, Ramazan Sarı, Kieran McCafferty, Borys Mankovsky, Sharon G. Adler, Linda P. Fried, Robert Toto, Mark V. Williams, Tran Quang Khanh, Diego Aizenberg, Inés Bartolacci, Diego Besada, Julio Bittar, Mariano Chahin, Alicia Elbert, Elizabeth Gelersztein, Alberto Liberman, Laura Maffei, Federico Pérez Manghi, Hugo Sanabria, Gloria Viñes, Alfredo Wassermann, Walter P. Abhayaratna, Shamasunder Acharya, Elif I. Ekinci, Darren Lee, Peak Mann Mah, Craig Nelson, David Packham, Alexia Pape, Simon D. Roger, Hugo Stephenson, Michael Suranyi, Gary Wittert, Elizabeth Vale, Martin Clodi, Christoph Ebenbichler, Evelyn Fließer-Görzer, Ursula Hanusch, Michael Krebs
Abstract
OBJECTIVE: Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS: Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30-5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin-angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS: Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS: Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.