Should I start an SGLT‑2 inhibitor in a patient with heart failure with preserved ejection fraction (HFpEF) who has an estimated glomerular filtration rate (eGFR) of 25 mL/min/1.73 m² and elevated pro‑BNP?

Yes, initiate an SGLT2 inhibitor now in this patient with HFpEF, eGFR 25 mL/min, and elevated pro-BNP.

Despite the eGFR of 25 mL/min being at the lower threshold, current guidelines support SGLT2 inhibitor initiation in HFpEF patients with eGFR ≥20 mL/min/1.73 m², and the elevated pro-BNP confirms the heart failure diagnosis that warrants treatment.

Guideline-Based Rationale

The 2022 Canadian Cardiovascular Society guidelines provide a Strong Recommendation with Moderate-Quality Evidence for SGLT2 inhibitors in adults with heart failure and LVEF >40% to reduce hospitalization for heart failure 1. The practical tip explicitly states these agents are not indicated for patients with eGFR <20 mL/min/1.73 m² but can be used above this threshold 1.

The 2022 KDIGO guidelines and ADA/KDIGO consensus report updated their initiation threshold to eGFR ≥20 mL/min/1.73 m² (changed from ≥25 mL/min/1.73 m² in earlier versions), driven by evidence from EMPEROR trials showing efficacy and safety for empagliflozin in patients with eGFR ≥20 mL/min/1.73 m² and heart failure 2. The evidence supporting initiation at eGFR 20-29 mL/min/1.73 m² is strongest for patients with concomitant heart failure 2, which applies directly to your patient.

Specific Agent Selection

Choose empagliflozin 10 mg daily based on:

• EMPEROR-Preserved trial demonstrated reduction in cardiovascular death or HF hospitalization (HR 0.79,95% CI 0.69-0.90) in HFpEF patients 1
• The trial included patients with eGFR ≥20 mL/min/1.73 m² 2
• Empagliflozin showed consistent benefit across the ejection fraction spectrum, though effects were attenuated when LVEF >65% 1

Alternative: Dapagliflozin 10 mg daily is also appropriate:

• FDA-approved for HFpEF with eGFR ≥25 mL/min/1.73 m² 3, 2
• Your patient at eGFR 25 meets this threshold exactly
• May continue even if eGFR falls below 25 during treatment 3

Critical Monitoring and Safety Considerations

Before Initiation:

• Volume status assessment: Check for concurrent diuretic use and signs of volume depletion 4, 2
• Serum potassium: Ensure normal before starting 4
• Educate on sick day protocol: Temporarily withhold during illness, excessive exercise, or alcohol intake 4

Expected eGFR Changes:

A reversible eGFR decline of up to 15% may occur within 1-3 months and is NOT an indication to discontinue 5, 4. The KDIGO guideline explicitly states: "Once an SGLT2i is initiated, it is reasonable to continue even if the eGFR falls below 20 mL/min per 1.73 m², unless it is not tolerated or kidney replacement therapy is initiated" 4.

Common Pitfalls to Avoid:

1. Do not stop for initial eGFR dip: This hemodynamic effect is expected and protective long-term 4, 2
2. Monitor for volume depletion: Consider proactive diuretic dose reduction if patient is on high-dose loop diuretics 2
3. Genital mycotic infections: Counsel on hygiene; occurs in ~10-15% of women, less in men 5, 2
4. Diabetic ketoacidosis risk: Though your patient's diabetes status isn't specified, educate on symptoms (nausea, vomiting, abdominal pain) and maintain sick day protocol 5, 2

Follow-Up Protocol

At 1-4 weeks:

• Reassess volume status and symptoms
• Check basic metabolic panel (creatinine, potassium)
• Adjust concomitant diuretics if needed

At 1-3 months:

• Repeat eGFR (expect potential 10-15% decline that should stabilize)
• Continue therapy unless intolerable side effects or dialysis initiation

Ongoing:

• Monitor for hypoglycemia if on insulin or sulfonylureas (adjust doses as needed) 2
• Assess for signs of volume depletion, especially during intercurrent illness

Contraindications That Do NOT Apply Here

Your patient does NOT have:

• Type 1 diabetes (contraindicated) 5
• Active dialysis (contraindicated) 3, 1
• eGFR <20 mL/min/1.73 m² (below initiation threshold) 1

Evidence Strength

The recommendation is based on:

• EMPEROR-Preserved trial: Landmark phase III RCT showing 21% reduction in HF hospitalization in HFpEF 1
• Pooled meta-analyses: Demonstrating 29% reduction in HF hospitalization across HFpEF populations 1
• Consistent benefit: Across diabetes status, age, NYHA class, and baseline renal function 6
• Recent 2025 pooled analysis: Confirmed SGLT2i benefits are maintained even after severe eGFR deterioration during follow-up 7

The elevated pro-BNP confirms significant heart failure pathophysiology that will benefit from SGLT2 inhibitor therapy, which has been shown to slow eGFR decline (3.3 vs 5.7 mL/min/1.73 m² per year, p<0.0001) 1 and reduce the composite kidney outcome 1.