ADA 2021. A prespecified subanalysis of FIDELIO-DKD found primary and secondary renal and CV endpoints consistent whether or not GLP-1 receptor agonists were on board at study baseline.
One of 3 predefined subanalyses of the FEDELIO-DKD study designed to assess potential interaction between finerenone and antidiabetes agents on board at study inception, the present analysis found that renal protection observed during the original study was consistent regardless of concomitant glucagon-like peptide-1 receptor agonist (GLP-1 RA) use.
Investigators also report no between-group interaction for the FIDELIO-CKD secondary cardiovascular (CV) outcomes. The reduction in UACR seen in the original study also was independent of GLP-1 RA use.
The new findings were released at the American Diabetes Association 81st Scientific Sessions which began June 25, 2021 and will wrap up tomorrow, June 29, 2021.
FIDELIO-DKD studied the effects of finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, in patients with chronic kidney disease (CKD) and T2D. The randomized controlled trial enrolled 5674 patients with T2D, UACR between 30-5000 mg/g, eGFR from 25-74 mL/min/1.73min2, and receiving optimized RAAS blockade. Participants were randomized to finerenone (10 mg daily increasing to 20 mg daily) or placebo.
The trial's primary kidney outcome was time to kidney failure, sustained eGFR decline ≥40% from baseline, or renal death. Secondary outcomes included time to CV death, non-fatal MI, non-fatal stroke, or hospitalization for heart failure, and change in UACR from baseline to month 4.
FIDELIO-CKD demonstrated that use of finerenone was associated with a reduction of 18% in risk for progression of CKD and a reduction of 16% in the secondary composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.
Lead author Peter Rossing, MD, DMSc, Head of Complications Research and Chief Physician at Steno Diabetes Center in Copenhagen and colleagues, report that of the original 5674-patient cohort, 394 (6.9%) were receiving a GLP-1 RA at baseline. Characteristics distinguishing GLP-1 RA recipients from other participants included: higher BMI measures and A1c levels at baseline, greater use of diuretics and statins, lower median urine albumin-to-creatinine ratio (UACR) and lower prevalence of cardiovascular disease (CVD).
Analysis of patients treated with finerenone with and without concomitant GLP-1 RA therapy found no between-group interaction for the primary kidney outcome (HR 1.17, 95% CI 0.71-1.90 with GLP-1RA; HR 0.80, 95% CI 0.71-0.91 without GLP-1RA; Pinteraction 0.15) or the secondary CV outcome (HR 1.02, 95% CI 0.60-1.74 with GLP-1RA; HR 0.85, 95% CI 0.73-0.98 without GLP-1RA; Pinteraction 0.51).
The current analysis, led by Peter Rossing, MD, DMSc, demonstrated no difference in results based on SGLT-2i use at baseline for the primary (pinteraction= 0.21) and key secondary (pinteraction=0.46), CV outcomes.
Rossing et al also report that use of finerenone was associated with a reduction in UACR (ratio of LS-means 0.68, 0.65-0.71; p<.0001) and that the reduction appeared to be greater among those also taking SGLT-2is at baseline (ratio of LS-means 0.75, 0.62-0.90; p=0.0024).
In a post-hoc analysis of treatment-emergent hyperkalemia events, incidence was similar in patients using GLP-1 RAs and those who were not.
Reference: Rossing P, Agarwal R, Anker S, et al. Efficacy and safety of finerenone in patients with CKD and T2D by GLP-1RA treatment. American Diabetes Association Presented Friday, June 25, 2021, 406-P.
Reference: Rossing P, Agarwal R, Anker S, et al. Finerenone in patients with CKD and T2D by SGLT2i treatment: an analysis of the FIDELIO-DKD study. American Diabetes Association Presented Friday, June 25, 2021, 14-LB--2021.
For a Patient Care Online conversation with FIDELIO-DKD lead investigator George Bakris, MD, please click here.
The original study, Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes was published in December 2020 in the New England Journal of Medicine.