Alternative Medications to Kerendia (Finerenone)
SGLT-2 inhibitors and GLP-1 receptor agonists are the preferred alternatives to Kerendia for patients with chronic kidney disease and type 2 diabetes, with SGLT-2 inhibitors being the strongest first-line recommendation for cardiorenal protection. 1, 2
Primary Alternatives: SGLT-2 Inhibitors
SGLT-2 inhibitors represent the most robust alternative, with strong guideline support for patients at higher risk of cardiovascular and kidney complications. These agents:
- Provide superior evidence for mortality benefit (high certainty evidence) compared to finerenone 1
- Can be used at eGFR as low as 20 mL/min/1.73 m² based on EMPA-KIDNEY trial data 2
- Demonstrate effectiveness even in patients with normal urinary albumin levels 2
- Show a 24% reduction in major kidney disease events (including >50% decline in eGFR, kidney failure, dialysis initiation, or cardiovascular death) 2
The 2025 BMJ guideline provides a strong recommendation in favor of SGLT-2 inhibitors for adults at higher risk, while giving only a weak recommendation against finerenone for moderate-risk patients 1. This represents a critical distinction in the strength of evidence.
Secondary Alternative: GLP-1 Receptor Agonists
GLP-1 receptor agonists serve as another evidence-based alternative:
- Carry the same strong recommendation as SGLT-2 inhibitors for high-risk patients 1
- Recently demonstrated kidney benefits in the FLOW study with semaglutide, showing 24% lower hazard ratio for major kidney events 2
- May be particularly valuable for patients with obesity who place greater value on weight reduction 1
- Can be used at low eGFR for cardiovascular protection, though may require dose adjustment 2
Combination Therapy Approach
Recent evidence supports that SGLT-2 inhibitors and GLP-1 receptor agonists preserve independent beneficial effects when used together, supporting combination therapy where appropriate 1. This is particularly relevant since:
- The CONFIDENCE trial showed additional proteinuria reduction when combining finerenone with empagliflozin (an SGLT-2 inhibitor) 3
- Both drug classes target different pathophysiologic mechanisms
Why These Are Superior to Finerenone
The 2025 guideline explicitly recommends against finerenone for moderate-risk CKD patients due to 1:
- Little or no mortality benefit (moderate to high certainty evidence)
- Risk of severe hyperkalemia (moderate certainty evidence)
- Limited clinical experience compared to SGLT-2 inhibitors
- Higher treatment burden and cost considerations
Finerenone showed only marginal cardiovascular and kidney benefits in the FIDELIO-DKD and FIGARO-DKD trials 1, 2, whereas SGLT-2 inhibitors demonstrated clear survival advantages.
Clinical Decision Algorithm
- First-line for high-risk patients: SGLT-2 inhibitor (strong recommendation)
- Add or substitute: GLP-1 receptor agonist if obesity is present or SGLT-2 inhibitor contraindicated
- Consider finerenone only: After maximizing SGLT-2 inhibitor and GLP-1 RA therapy, or if these are contraindicated
- Monitor closely: Serum potassium if using finerenone (hyperkalemia risk 14% vs 6.9% placebo) 4
Important Caveats
- Hyperkalemia monitoring is critical with any mineralocorticoid receptor antagonist, including finerenone, which led to permanent discontinuation in 1.7% of patients 4
- SGLT-2 inhibitors cause initial small decreases in eGFR (2-3 mL/min) that stabilize, similar to finerenone 2, 4
- For treatment-resistant hypertension specifically, classic steroidal MRAs (spironolactone, eplerenone) may still have value 3
- Avoid grapefruit juice and strong CYP3A4 inhibitors if finerenone is ultimately used 4
The evidence hierarchy clearly positions SGLT-2 inhibitors as the preferred alternative, with GLP-1 receptor agonists as a complementary or alternative option, both supported by stronger outcome data than finerenone for cardiorenal protection.