Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Sodium-Glucose Cotransporter 2 Inhibitor Treatment: The FIDELITY Analysis

Abstract

Objective: Finerenone reduced the risk of kidney and cardiovascular events in people with chronic kidney disease (CKD) and type 2 diabetes in the FIDELIO-DKD and FIGARO-DKD phase 3 studies. Effects of finerenone on outcomes in patients taking sodium-glucose cotransporter 2 inhibitors (SGLT2is) were evaluated in a prespecified pooled analysis of these studies.

Research design and methods: Patients with type 2 diabetes and urine albumin-to-creatinine ratio (UACR) ≥30 to ≤5,000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 were randomly assigned to finerenone or placebo; SGLT2is were permitted at any time. Outcomes included cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% eGFR decline, or renal death) end points, changes in UACR and eGFR, and safety outcomes.

Results: Among 13,026 patients, 877 (6.7%) received an SGLT2i at baseline and 1,113 (8.5%) initiated one during the trial. For the cardiovascular composite, the hazard ratios (HRs) were 0.87 (95% CI 0.79-0.96) without SGLT2i and 0.67 (95% CI 0.42-1.07) with SGLT2i. For the kidney composite, the HRs were 0.80 (95% CI 0.69-0.92) without SGLT2i and 0.42 (95% CI 0.16-1.08) with SGLT2i. Baseline SGLT2i use did not affect risk reduction for the cardiovascular or kidney composites with finerenone (Pinteraction = 0.46 and 0.29, respectively); neither did SGLT2i use concomitant with study treatment.

Conclusions: Benefits of finerenone compared with placebo on cardiorenal outcomes in patients with CKD and type 2 diabetes were observed irrespective of SGLT2i use.

Figure 1

Analysis of kidney and cardiovascular composite outcomes in patients receiving or not receiving an SGLT2i at baseline and in patients receiving or not receiving an SGLT2i at any time during the on-treatment period. Shown are adjusted *HRs for HbA_1c, SBP, and UACR at baseline (log-transformed) and eGFR at baseline. †P_interaction is based on a stratified Cox proportional hazards model including treatment, subgroup, the additional covariates, and treatment-by-subgroup interaction. ‡Comedication use is defined as exposure to comedication in the on-treatment period (i.e., a patient can contribute to the use and nonuse categories based on the actual exposure time with and without comedication). §HR and P_interaction are based on a stratified Cox model including treatment as simple and comedication use as time-varying covariates as well as their interaction and the additional covariates. eGFR, estimated glomerular filtration rate; HR, hazard ratio; PY, patient-years; SBP, systolic blood pressure; SGLT2i, sodium–glucose cotransporter 2 inhibitor; UACR, urine albumin-to-creatinine ratio.

Figure 2

Change in UACR over time in patients receiving or not receiving an SGLT2i at baseline. Mixed model with factors included treatment group, region, eGFR category at screening, type of albuminuria at screening, time, treatment-by-time interaction, log-transformed baseline value nested within type of albuminuria at screening, and log-transformed baseline value-by-time interaction as covariates. eGFR, estimated glomerular filtration rate; IQR, interquartile range; SGLT2i, sodium–glucose cotransporter 2 inhibitor; UACR, urine albumin-to-creatinine ratio.