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Randomized Controlled Trial
. 2024 Mar 1;47(3):362-370.
doi: 10.2337/dc23-1420.

Outcomes With Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Baseline Insulin Resistance

Thomas Ebert  1 , Stefan D Anker  2 , Luis M Ruilope  3   4   5 , Paola Fioretto  6 , Vivian Fonseca  7 , Guillermo E Umpierrez  8 , Andreas L Birkenfeld  9   10   11 , Robert Lawatscheck  12 , Charlie Scott  13 , Katja Rohwedder  14 , Peter Rossing  15   16 ; FIDELIO-DKD and FIGARO-DKD Investigators
Affiliations
Randomized Controlled Trial

Outcomes With Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Baseline Insulin Resistance

Thomas Ebert et al. Diabetes Care. .

Abstract

Objective: To explore whether insulin resistance, assessed by estimated glucose disposal rate (eGDR), is associated with cardiorenal risk and whether it modifies finerenone efficacy.

Research design and methods: In FIDELITY (N = 13,026), patients with type 2 diabetes, either 1) urine albumin-to-creatinine ratio (UACR) of ≥30 to <300 mg/g and estimated glomerular filtration rate (eGFR) of ≥25 to ≤90 mL/min/1.73 m2 or 2) UACR of ≥300 to ≤5,000 mg/g and eGFR of ≥25 mL/min/1.73 m2, who also received optimized renin-angiotensin system blockade, were randomized to finerenone or placebo. Outcomes included cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (kidney failure, sustained decrease of ≥57% in eGFR from baseline, or renal death) composites. eGDR was calculated using waist circumference, hypertension status, and glycated hemoglobin for 12,964 patients.

Results: Median eGDR was 4.1 mg/kg/min. eGDR <median (insulin resistant) was associated with higher cardiovascular event incidence regardless of treatment versus ≥median (insulin sensitive) (incidence rate/100 patient-years of 5.18 and 6.34 [for finerenone and placebo] vs. 3.47 and 3.76 [for finerenone and placebo], respectively). However, eGDR was not associated with kidney outcomes. There was no significant heterogeneity for effects of finerenone by eGDR on cardiovascular (<median: hazard ratio [HR] 0.81, 95% CI 0.72-0.92; ≥median: HR = 0.92, 95% CI 0.79-1.06; P interaction = 0.23) or kidney outcomes (<median: HR = 0.84, 95% CI 0.68-1.02; ≥median: HR = 0.70, 95% CI 0.58-0.85; P interaction = 0.28). Overall, finerenone demonstrated similar safety between subgroups. Sensitivity analyses were consistent.

Conclusions: Insulin resistance was associated with increased cardiovascular (but not kidney) risk and did not modify finerenone efficacy.

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Conflict of interest statement

Duality of Interest. T.E. has served as a paid consultant for Bayer, Lilly Deutschland, and Sanofi and reports personal fees from Bayer, Fresenius Medical Care Deutschland, Lilly Deutschland, Novo Nordisk, Sanofi, and Santis Pharmaceuticals. He has received research support from the European Foundation for the Study of Diabetes (EFSD Mentorship Programme supported by AstraZeneca) and Otsuka Pharma. S.D.A. reports grants and personal fees from Vifor and Abbott Vascular, and personal fees for consultancies, trial committee work, and/or lectures from Actimed, Amgen, AstraZeneca, Bayer, Bioventrix, Boehringer Ingelheim, B R A H M S, Cardiac Dimensions, Cardior, Cordio, CVRx, Edwards, Faraday, Impulse Dynamics, Janssen, Novartis, Occlutech, Pfizer, Respicardia, Servier, Vectorious, and V-Wave. He is named co-inventor of two patent applications regarding MR-proANP (DE 102007010834 and DE 102007022367), but he does not benefit personally from the related issued patents. L.M.R. reports receipt of consultancy fees from Bayer. P.F. reports consultation fees from AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Mundipharma, and Novo Nordisk. V.F. has served as a paid consultant for Abbott, Asahi, AstraZeneca, Bayer, Novo Nordisk, and Sanofi. He has patent and ownership interests in BRAVO4Health. G.E.U. has received research support (to Emory University) from Abbott, Bayer, and Dexcom Inc. A.L.B. reported research support from Boehringer Ingelheim and personal fees from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. All fees are given to Tübingen University. R.L. is a full-time employee of Bayer AG, Division Pharmaceuticals, Germany. C.S. is a full-time employee of Bayer PLC, Division Pharmaceuticals, U.K. K.R. is a full-time employee of Bayer AG. P.R. reported personal fees from Bayer during the conduct of the study. He has received research support and personal fees from AstraZeneca, Bayer, and Novo Nordisk and personal fees from Abbott, Astellas, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, and Sanofi, and all fees are given to Steno Diabetes Center Copenhagen. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
CV and kidney composite outcomes by eGDR subgroups (P value was based on a stratified Cox proportional hazards model including treatment, subgroup, and treatment by subgroup interaction. All Cox proportional hazards models were adjusted for blood pressure (systolic), sex, HbA1c at baseline, and diabetes duration. CV composite outcome denotes the of time to first onset of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; kidney composite outcome denotes the of time to first onset of kidney failure, sustained ≥57% decrease in eGFR from baseline over ≥4 weeks, or renal death.
Figure 2
Figure 2
CV (A) and ≥57% kidney composite (B) outcomes by continuous variable eGDR.
See this image and copyright information in PMC

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