What are the benefits of finerenone (Mineralocorticoid Receptor Antagonist) for patients with Type 2 Diabetes (T2D)?

Benefits of Finerenone for Type 2 Diabetes

Finerenone provides dual cardiovascular and kidney protection in patients with type 2 diabetes and chronic kidney disease, reducing cardiovascular events by 14% and kidney failure by 23%, and should be added to maximally tolerated renin-angiotensin system inhibitors in patients with persistent albuminuria (≥30 mg/g) and eGFR ≥25 mL/min/1.73 m². 1, 2, 3

Primary Cardiovascular Benefits

Finerenone delivers substantial cardiovascular protection through multiple mechanisms:

• Reduces composite cardiovascular outcomes (cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization) by 14% (HR 0.86,95% CI 0.78-0.95) across the spectrum of chronic kidney disease 4, 3

• Decreases heart failure hospitalizations by 29% (HR 0.71,95% CI 0.56-0.90), with particular benefit in preventing new-onset heart failure in patients without symptomatic HFrEF 1, 4

• Lowers cardiovascular mortality risk by 16% (HR 0.84,95% CI 0.74-0.95) in the pooled FIDELITY analysis of 13,026 patients 5

The cardiovascular benefits are consistent regardless of whether patients have established atherosclerotic cardiovascular disease at baseline 6.

Kidney Protection Benefits

Finerenone provides robust renoprotection that complements SGLT2 inhibitors:

• Reduces composite kidney outcomes by 23% (HR 0.77,95% CI 0.67-0.88), including kidney failure, sustained ≥57% decrease in eGFR, or renal death 2, 3

• Decreases progression to end-stage kidney disease by 36% (HR 0.64,95% CI 0.41-0.995) 4

• Reduces albuminuria in patients with type 2 diabetes and CKD, addressing a key marker of kidney disease progression 2

These kidney benefits were demonstrated in the FIDELIO-DKD trial specifically designed to assess renal outcomes in patients with stage 3-4 CKD and severe albuminuria 1.

Patient Selection Criteria

The ideal candidates for finerenone therapy have specific characteristics:

• Type 2 diabetes with CKD and persistent albuminuria (UACR ≥30 mg/g) despite maximum tolerated renin-angiotensin system inhibitor therapy 2, 4

• eGFR ≥25 mL/min/1.73 m² at baseline 1, 2, 4

• Serum potassium ≤4.8 mmol/L before initiation 2, 4

Notably, 40% of patients in the FIDELITY analysis had eGFR >60 mL/min/1.73 m², demonstrating benefit even in earlier stages of CKD identified solely by albuminuria 3.

Dosing Strategy

Dose finerenone based on kidney function:

• 10 mg once daily for patients with eGFR 25-60 mL/min/1.73 m² 2, 4

• 20 mg once daily for patients with eGFR >60 mL/min/1.73 m² 2, 4

• Uptitrate to 20 mg daily after 4 weeks if serum potassium remains <4.8 mmol/L in patients started on 10 mg 2

Treatment Sequencing Algorithm

The American Diabetes Association and KDOQI guidelines recommend a specific sequence:

1. Maximize renin-angiotensin system inhibitor (ACE inhibitor or ARB) first 2

2. Add SGLT2 inhibitor as the preferred next step due to larger effects on both kidney and cardiovascular outcomes 2

3. Consider finerenone if albuminuria persists despite SGLT2 inhibitor therapy, or if SGLT2 inhibitor is not tolerated 2

4. Triple therapy with RAS inhibitor + SGLT2 inhibitor + finerenone may provide complementary cardiorenal protection 2, 4

This sequencing prioritizes SGLT2 inhibitors over finerenone initially, but recognizes finerenone's role when albuminuria remains despite optimal therapy 2.

Combination with Other Cardioprotective Agents

Finerenone can be used alongside other diabetes medications:

• Compatible with SGLT2 inhibitors with potentially additive benefits for kidney protection 7, 4

• Can be added to GLP-1 receptor agonists as part of comprehensive cardiovascular risk reduction 4

• Should be used with metformin as most trial patients were on metformin at baseline 1

The American Heart Association endorses this combination approach as part of comprehensive cardiorenal protection strategy 7.

Safety Profile and Monitoring

Hyperkalemia is the primary adverse effect, occurring in 10.8-14% of finerenone patients versus 5.3-6.9% with placebo 4, 5:

• Check potassium at baseline, 4 weeks after initiation, and every 4 months during maintenance 2, 4

• If potassium 4.9-5.5 mmol/L: Continue current dose and monitor every 4 months 2

• If potassium >5.5 mmol/L: Hold finerenone, adjust diet/medications, restart at 10 mg when potassium ≤5.0 mmol/L 2

• Permanent discontinuation due to hyperkalemia occurs in only 1.7% of patients versus 0.6% with placebo 3

Overall safety outcomes are generally similar between finerenone and placebo, with no significant difference in total adverse events 8.

Clinical Context and Pitfalls

Common pitfall: Failing to screen for albuminuria in type 2 diabetes patients with normal or mildly reduced eGFR. Since 40% of FIDELITY patients had eGFR >60 mL/min/1.73 m², albuminuria screening is essential to identify at-risk patients who would benefit from finerenone 3.

Important caveat: While finerenone reduces cardiovascular and kidney outcomes, it should be positioned after SGLT2 inhibitors in the treatment algorithm unless SGLT2 inhibitors are contraindicated or not tolerated 2. The combination of both agents may provide optimal cardiorenal protection in high-risk patients with persistent albuminuria 2, 4.