What is finerenone?

What is Finerenone

Finerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist (MRA) indicated for adults with type 2 diabetes and chronic kidney disease (CKD) who have persistent albuminuria despite maximum tolerated renin-angiotensin system inhibitor therapy, providing proven cardiovascular and kidney protection. 1, 2

Drug Classification and Mechanism

• Finerenone is a third-generation, nonsteroidal MRA with higher selectivity for the mineralocorticoid receptor compared to steroidal MRAs like spironolactone and stronger receptor-binding affinity than eplerenone 3
• It is currently the only nonsteroidal MRA with proven clinical kidney and cardiovascular benefits in randomized controlled trials 1
• The nonsteroidal structure provides greater MR selectivity, which may reduce the risk of hyperkalemia compared to traditional steroidal MRAs 3

Clinical Indications

• Primary indication: Adults with type 2 diabetes and CKD who have persistent albuminuria (ACR ≥30 mg/g) despite maximum tolerated doses of ACE inhibitors or ARBs, with eGFR ≥25 mL/min/1.73 m² and serum potassium <4.8 mmol/L 1, 2
• Finerenone is positioned as second-line cardiorenal protection after SGLT2 inhibitors, or as add-on therapy for patients with persistent albuminuria despite SGLT2 inhibitor use 4, 2

Dosing Strategy

• Starting dose: 10 mg once daily for patients with eGFR 25-60 mL/min/1.73 m² 1, 2
• Starting dose: 20 mg once daily for patients with eGFR >60 mL/min/1.73 m² 1, 2
• Dose escalation: Increase from 10 mg to 20 mg daily after 4 weeks if serum potassium remains ≤4.8 mmol/L and eGFR is stable 1, 2
• Continue treatment until dialysis or transplantation 1

Cardiovascular Benefits

• Reduces composite cardiovascular outcomes (cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure) by 13-14% (HR 0.86-0.87) 1, 4
• Reduces heart failure hospitalization by 29% (HR 0.71,95% CI 0.56-0.90), which was the primary driver of cardiovascular benefit 4, 5
• These benefits were demonstrated in the FIGARO-DKD trial over a median follow-up of 3.4 years 5

Kidney Protection Benefits

• Reduces CKD progression by 23% (composite of kidney failure, sustained ≥40-57% decrease in eGFR, or renal death; HR 0.77-0.82) 1, 6
• Reduces kidney failure requiring dialysis or transplantation by 20-36% (HR 0.64-0.80) 1
• Reduces albuminuria in patients with type 2 diabetes and CKD 6
• These benefits were demonstrated in the FIDELIO-DKD trial over a median follow-up of 2.6 years 6

Safety Profile and Monitoring

• Hyperkalemia risk: Occurs in 10.8-14% of patients on finerenone versus 5.3-6.9% on placebo 1, 4
• Discontinuation rate: Only 1.2-2.3% of patients discontinue due to hyperkalemia versus 0.4-0.9% on placebo 1, 6, 5
• No deaths from hyperkalemia were reported over 3 years of follow-up 1
• Monitoring protocol: Check serum potassium at baseline and after 4 weeks of treatment 4, 2
• Management of hyperkalemia: If potassium rises >5.5 mmol/L, withhold finerenone and restart at 10 mg daily when potassium ≤5.0 mmol/L 2

Therapeutic Positioning in Treatment Algorithm

• KDIGO 2022 and American Diabetes Association 2023 guidelines establish a clear hierarchy: SGLT2 inhibitors are first-line cardiorenal protection, with finerenone as second-line for patients with persistent albuminuria 1, 4
• Finerenone should be considered if a patient does not tolerate an SGLT2 inhibitor or remains with albuminuria despite SGLT2 inhibitor therapy 2
• Finerenone may be added to both a renin-angiotensin system inhibitor and an SGLT2 inhibitor for complementary cardiorenal protection 2
• The American Heart Association supports combining finerenone with SGLT2 inhibitors for potentially additive benefits 4

Evidence Base

• The FIDELIO-DKD trial (N=5,734) demonstrated kidney protection in patients with more advanced CKD (eGFR 25-75 mL/min/1.73 m² and higher albuminuria) 6
• The FIGARO-DKD trial (N=7,437) demonstrated cardiovascular protection in patients with earlier CKD (eGFR 25-90 mL/min/1.73 m² and moderate albuminuria) 5
• The FIDELITY pooled analysis (N=13,171) confirmed benefits across the full spectrum of CKD severity 1