Why are Sodium-Glucose Linked Transporter 2 (SGLT2) medications prescribed to non-diabetic patients with heart failure?

SGLT2 Inhibitors in Non-Diabetic Patients with Heart Failure

SGLT2 inhibitors are strongly recommended for non-diabetic patients with heart failure to reduce cardiovascular death, heart failure hospitalizations, and improve quality of life, regardless of diabetes status. 1

Mechanism and Evidence Base

SGLT2 inhibitors were initially developed as glucose-lowering medications for type 2 diabetes, but their cardiovascular benefits have been shown to be independent of their glucose-lowering effects. Major clinical trials have demonstrated significant benefits in heart failure patients regardless of diabetes status:

• Heart Failure with Reduced Ejection Fraction (HFrEF):

  • DAPA-HF and EMPEROR-Reduced trials showed that dapagliflozin and empagliflozin reduced the composite of cardiovascular death or heart failure hospitalization by approximately 25% 1
  • Benefits were consistent in patients with and without diabetes 1
  • The reduction in heart failure hospitalization was even greater (30%) in both trials 1

• Heart Failure with Preserved Ejection Fraction (HFpEF):

  • EMPEROR-Preserved trial demonstrated benefits in patients with LVEF >40% 2
  • PRESERVED-HF showed dapagliflozin leads to significant improvement in both symptoms and physical limitations in HFpEF patients regardless of diabetes status 1

Clinical Application Algorithm

1. Patient Selection:

   • Patients with symptomatic heart failure (NYHA class II-IV)
   • LVEF ≤40% (HFrEF) - strongest recommendation (Class I) 1
   • LVEF >40% (HFpEF) - beneficial (Class 2a) 1
   • eGFR ≥20-30 mL/min/1.73 m² (depending on specific agent) 1

2. Recommended Agents:

   • Empagliflozin 10 mg daily
   • Dapagliflozin 10 mg daily
   • Sotagliflozin (SGLT1/2 inhibitor) - showed benefits but not yet FDA approved as of 2021 1

3. Expected Benefits:

   • Reduced risk of heart failure hospitalization
   • Reduced cardiovascular mortality
   • Improved symptoms and quality of life
   • Slower decline in renal function 1

4. Monitoring:

   • Blood pressure (potential for hypotension)
   • Renal function
   • Signs of genital infections
   • Volume status (may need diuretic adjustment)

Important Clinical Considerations

• Add, Don't Replace: SGLT2 inhibitors should be added to guideline-directed medical therapy including ACE inhibitors/ARBs, beta-blockers, and MRAs, not used as replacement 1

• No Dose Titration Required: Unlike many heart failure medications, SGLT2 inhibitors do not require dose titration, simplifying the treatment regimen 3

• Renal Benefits: SGLT2 inhibitors also provide nephroprotection, with reduced risk of serious renal outcomes and slower decline in eGFR 4

• Prevention Benefit: In patients with type 2 diabetes and asymptomatic stage B heart failure or high cardiovascular risk, SGLT2 inhibitors are recommended to prevent progression to symptomatic heart failure 1

Potential Side Effects and Precautions

• Genital Infections: Increased risk, particularly in women
• Volume Depletion: May require adjustment of diuretic doses
• Euglycemic Ketoacidosis: Rare but serious risk, especially in diabetic patients
• Hypotension: Monitor blood pressure, especially when initiating therapy

Conclusion

The evidence strongly supports the use of SGLT2 inhibitors in non-diabetic patients with heart failure, representing a paradigm shift in heart failure management. These medications have evolved from diabetes treatments to essential components of heart failure therapy, with benefits on mortality, hospitalizations, and quality of life that are independent of glucose-lowering effects.