Efficacy of finerenone in reducing proteinuria in diabetic kidney disease on dapagliflozin and telmisartan: A disease-modifying approach

Table 1 Trials showing benefits of finerenone in diabetes kidney disease

Trial name	No of Subjects (T2DM on maximally tolerated ACEi/ARB)	Follow up	Renal outcomes (kidney failure, more than 40 percentage decrease in eGFR from baseline, or renal death)	CV outcome (cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization)	Reduction of UACR from baseline to month 4
FIDELIO-DKD[20]	5734	2.6 years	17.8 percentage with finerenone vs 21.1 percentage with placebo (HR = 0.82, 95%CI: 0.73-0.93; P = 0.001)	13.0 percentage with finerenone vs 14.8 percentage with placebo (HR = 0.86, 95%CI: 0.75-0.99; P = 0.03)	31% greater reduction than placebo [ratio of least-squares mean change from baseline (finerenone vs placebo), 0.69; 95%CI: 0.66-0.71]
FIGARO-DKD[21]	7437	3.4 years	9.5 percentage with finerenone vs 10.8 percentage with placebo (HR = 0.87, 95%CI: 0.76-1.01; P = 0.07)	12.4 percentage with finerenone vs 14.2 percentage with placebo (HR = 0.87, 95%CI: 0.76-0.98; P = 0.03)	32% greater reduction with finerenone than with placebo (ratio of the least-squares mean change from baseline, 0.68; 95%CI: 0.65-0.70)

ACEi: Angiotensin convertase enzyme inhibitor; ARB: Angiotensin receptor blocker; CV: Cardiovascular; eGFR: Estimated glomerular filtration rate; HR: Hazards ratio; MI: Myocardial infarction; T2DM: Type 2 diabetes mellitus.

Table 2 Comparison of third-generation non-steroidal mineralocorticoid receptor antagonists

Characteristic features	Finerenone	Esaxerenone	Apararenone (MT-3995)
Primary clinical indication	Diabetic kidney disease (2021-Food and Drug Administration of the United States, 2022-European Medicines Agency)	Hypertension; diabetic nephropathy (Japan)[45]	Diabetic nephropathy (investigational)[46]
Relative potency in MR antagonism to Spironolactone	Similar. Specific affinity for MR receptor	Higher	Lesser
Half-life (t1/2). Active metabolites	2-3 hours. None	30 hours. Not clinically relevant	275-285 hours
Tissue distribution (rodent studies)[41]	Balanced (heart = kidney)	Balanced (heart = kidney)	Balanced (heart = kidney)
BP lowering effect	Modest	Potent	Potent
Hyperkalemia risk	Less compared to steroidal MRA. Can start when blood potassium ≤ 4.8 - > 5.0 mmol/L	higher rate compared with eplerenone (ESAX-HTN)[44]	Minor risk
Blood-brain barrier	Does not cross	Crosses	Likely crosses
Dose schedule	eGFR ≥ 60 mL/minute/1.73 m2: 20 mg/day; eGFR 25-59 mL/minute/1.73 m2: 10 mg/day; eGFR < 25 mL/minute/1.73 m2: Not recommended	1.25-2.5 mg/day	2.5, 5, 10 mg/day

BP: Blood pressure; eGFR: Estimated glomerular filtration rate; MRA: Mineralocorticoid receptor antagonists.