What is the recommended dosage for Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors in patients with heart failure?

SGLT2 Inhibitor Dosing for Heart Failure Patients

For patients with heart failure, SGLT2 inhibitors should be initiated at the following doses: dapagliflozin 10 mg once daily, empagliflozin 10 mg once daily, or canagliflozin 100 mg once daily. These medications can be used regardless of diabetes status and should be continued even if eGFR declines below initiation thresholds, as long as the patient tolerates the medication and is not on dialysis 1.

Specific SGLT2 Inhibitor Dosing Guidelines

Dapagliflozin

• Standard dose: 10 mg once daily 1
• eGFR considerations:
  • Can be initiated with eGFR ≥25 mL/min/1.73 m² 1
  • Can be continued if eGFR falls below 25 mL/min/1.73 m² in patients with heart failure 1
  • Contraindicated in dialysis 1

Empagliflozin

• Standard dose: 10 mg once daily 1
• eGFR considerations:
  • Can be initiated with eGFR ≥20 mL/min/1.73 m² for heart failure 1
  • Not recommended for initiation with eGFR <20 mL/min/1.73 m² 1
  • Contraindicated in dialysis 1

Canagliflozin

• Standard dose: 100 mg once daily before first meal 1
• eGFR considerations:
  • For eGFR 30-60 mL/min/1.73 m²: 100 mg daily 1
  • For eGFR <30 mL/min/1.73 m² with albuminuria >300 mg/day: 100 mg daily 1
  • Not recommended for initiation if eGFR <30 mL/min/1.73 m² without albuminuria 1
  • Contraindicated in dialysis 1

Clinical Benefits and Evidence

• SGLT2 inhibitors significantly reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF), regardless of diabetes status 2, 3
• Benefits are seen early after initiation (within days to weeks) and maintained during long-term therapy 4, 5
• In the DAPA-HF trial, dapagliflozin 10 mg daily reduced the primary composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85) 2
• In the EMPEROR-Reduced trial, empagliflozin 10 mg daily showed similar benefits with a 25% reduction in the primary composite outcome 3
• SGLT2 inhibitors also reduce the need for loop diuretic dose adjustments in approximately 29% of patients within 60 days of initiation 6

Practical Considerations for Initiation

• No dose titration is required for SGLT2 inhibitors in heart failure patients - start with the standard dose 1
• Monitor for volume depletion, especially in patients with renal impairment, low systolic blood pressure, elderly patients, or those on diuretics 1
• Consider reducing the dose of concurrent diuretics if signs of volume depletion occur 6
• Continue therapy even if eGFR falls below initiation thresholds, as cardiovascular benefits persist 1
• SGLT2 inhibitors can be used as early, first-line therapy in patients with newly diagnosed HFrEF 4

Cautions and Monitoring

• Monitor for genital mycotic infections, which occur in approximately 6% of patients 1
• Be vigilant for euglycemic ketoacidosis, especially in patients with diabetes requiring insulin 1
• Consider pausing SGLT2 inhibitors during periods of acute illness or physiological stress 1
• Monitor renal function, but note that a mild, reversible decline in eGFR is expected and does not require discontinuation 1
• Canagliflozin has been associated with increased risk of amputation and bone fractures; use with caution in patients with peripheral vascular disease, neuropathy, or diabetic foot ulcers 1

Key Takeaways

• SGLT2 inhibitors should be used in heart failure patients with eGFR ≥20 mL/min/1.73 m² regardless of diabetes status 1
• Standard doses are dapagliflozin 10 mg daily, empagliflozin 10 mg daily, or canagliflozin 100 mg daily 1
• Benefits on heart failure outcomes appear as a class effect across different SGLT2 inhibitors 3
• Continue therapy even if eGFR declines below initiation thresholds, as long as the patient tolerates the medication 1
• Monitor for volume depletion and consider adjusting diuretic doses if needed 6