How to prescribe Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) for a patient with heart failure?

From the Guidelines

SGLT2 inhibitors (SGLT2i) are recommended for heart failure patients regardless of diabetes status, as they reduce hospitalizations and mortality, with the most recent evidence from 2024 supporting their use in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) 1. When prescribing SGLT2i for a patient with heart failure, consider the following:

• Start with dapagliflozin 10mg once daily or empagliflozin 10mg once daily, as these are the two agents with the strongest evidence in heart failure 1.
• Before initiating, check renal function (eGFR should be >20-30 ml/min/1.73m²), assess volume status, and review current medications 1.
• Counsel patients about potential side effects including genital mycotic infections, urinary tract infections, and volume depletion 1.
• Advise temporary discontinuation during acute illness, surgery, or situations with reduced oral intake to prevent euglycemic diabetic ketoacidosis 1.
• Monitor renal function after initiation, though these medications are generally renoprotective 1. Key benefits of SGLT2i in heart failure patients include:
• Reduction in hospitalizations and mortality 1
• Improvement in cardiac metabolism and energy efficiency 1
• Anti-inflammatory effects and reduction in cardiac fibrosis 1
• Renoprotective effects, with a decrease in the slope of the eGFR decline 1

From the FDA Drug Label

DAPAGLIFLOZIN tablets, for oral use ... INDICATIONS AND USAGE DAPAGLIFLOZIN TABLETS a sodium-glucose cotransporter 2 (SGLT2) inhibitor, are indicated: • To reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression (1) • To reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure. (1) ... DOSAGE AND ADMINISTRATION • Assess renal function prior to initiation and then as clinically indicated. Assess volume status and correct volume depletion before initiating. (2. 1) • For all other indications, the recommended dosage is 10 mg orally once daily. (2.3)

To prescribe Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i), such as dapagliflozin, for a patient with heart failure, the recommended dosage is 10 mg orally once daily.

• Assess renal function prior to initiation and then as clinically indicated.
• Assess volume status and correct volume depletion before initiating.
• The dosage may need to be adjusted based on renal impairment, as indicated in the full prescribing information 2.
• It is essential to monitor patients for potential side effects, such as ketoacidosis, and discontinue the medication if suspected.
• Contraindications include a history of serious hypersensitivity reaction to dapagliflozin or any of the excipients in DAPAGLIFLOZIN TABLETS.

From the Research

Prescribing SGLT2 Inhibitors for Heart Failure

To prescribe Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) for a patient with heart failure, consider the following:

• The patient's left ventricular ejection fraction (LVEF) and whether they have heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) 3, 4, 5
• The presence or absence of type 2 diabetes mellitus (T2DM), as SGLT2 inhibitors have been shown to be beneficial in patients with and without T2DM 4, 6, 7
• The patient's eligibility for SGLT2 inhibitors according to the entry criteria of clinical trials such as DAPA-HF and EMPEROR-Reduced, and US Food and Drug Administration (FDA) label criteria 3

Patient Eligibility

• A study found that 45% of patients with HFrEF would be candidates for initiation of both dapagliflozin and empagliflozin, and 86% would be eligible for dapagliflozin according to FDA label criteria 3
• The major determinant of ineligibility was the failure to achieve the predefined NT-proBNP inclusion threshold 3

Clinical Benefits

• SGLT2 inhibitors such as empagliflozin have been shown to reduce the risk of cardiovascular death or hospitalization for heart failure, and improve health-related quality of life in patients with symptomatic chronic heart failure 4, 6, 7
• Empagliflozin has been found to be beneficial in patients with acute de novo or decompensated chronic heart failure, regardless of left ventricular ejection fraction or the presence or absence of diabetes 7

Treatment Considerations

• SGLT2 inhibitors can be initiated in patients hospitalized for acute heart failure, and have been shown to be well tolerated and effective in improving clinical outcomes 7
• The role of ejection fraction in determining the effectiveness of SGLT2 inhibitors in patients with HFpEF is still being researched, and future studies should consider the dynamic nature of EF over time and use low-variability imaging techniques such as CMR 5