Which is more effective in treating heart failure with preserved ejection fraction, dapagliflozin or a Glucagon-like peptide-1 (GLP-1) receptor agonist?

Dapagliflozin is More Effective Than GLP-1 Receptor Agonists for Heart Failure with Preserved Ejection Fraction

For treating heart failure with preserved ejection fraction (HFpEF), dapagliflozin is more effective than GLP-1 receptor agonists based on robust clinical evidence demonstrating significant reductions in heart failure hospitalizations and improved clinical outcomes.

Evidence Supporting SGLT2 Inhibitors in HFpEF

Clinical Trial Evidence

• The DELIVER trial demonstrated that dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death by 18% in patients with HFpEF (LVEF >40%) (HR 0.82; 95% CI 0.73-0.92; P<0.001) 1
• Dapagliflozin specifically reduced worsening heart failure events by 21% (HR 0.79; 95% CI 0.69-0.91) in patients with preserved ejection fraction 1
• Similarly, empagliflozin in the EMPEROR-Preserved trial showed a 21% reduction in the composite of cardiovascular death or hospitalization for heart failure in adults with HFpEF (LVEF >40%) 2

Guideline Recommendations

• The 2022 AHA/ACC/HFSA guideline provides a Class 2a recommendation (moderate strength) for SGLT2 inhibitors in HFpEF 3
• The American College of Cardiology specifically recommends dapagliflozin for improving symptoms, physical function, and reducing hospitalization and cardiovascular death in HFpEF 4

Limited Evidence for GLP-1 Receptor Agonists in HFpEF

• Current guidelines and clinical trial evidence do not support the use of GLP-1 receptor agonists specifically for HFpEF treatment 3, 4
• The 2025 American Diabetes Association standards of care note that no significant reduction in heart failure hospitalization has been identified in cardiovascular outcomes trials of GLP-1 receptor agonists including lixisenatide, liraglutide, semaglutide, exenatide, albiglutide, or dulaglutide 3

Clinical Benefits of Dapagliflozin in HFpEF

• Improves symptoms and physical limitations as measured by the Kansas City Cardiomyopathy Questionnaire (improvement of 5.8 points at 12 weeks) 4
• Increases exercise capacity (8.2% improvement in 6-minute walk distance) 4
• Reduces total heart failure events and symptom burden 1
• Benefits are consistent regardless of diabetes status 1
• Benefits are similar among patients with LVEF ≥60% and those with LVEF <60% 1
• Implementation of dapagliflozin could translate to an absolute risk reduction of 1.3% for mortality and 5.1% for HF readmission within one year 5

Practical Considerations for Dapagliflozin Use

Dosing and Patient Selection

• Recommended dose: 10 mg once daily 4
• Appropriate for patients with HFpEF (LVEF >40%), with or without diabetes 4
• Can be used in patients with eGFR as low as 20 mL/min/1.73m² 4

Safety Profile

• Similar incidence of adverse events compared to placebo 1
• Key monitoring needs:
  • Genital mycotic infections
  • Urinary tract infections
  • Volume depletion/hypotension
  • Rare but serious risk of euglycemic diabetic ketoacidosis, particularly with insulin dose reduction, prolonged fasting, or carbohydrate restriction 3, 4

Treatment Algorithm for HFpEF

1. First-line therapy: SGLT2 inhibitor (dapagliflozin 10 mg daily) regardless of diabetes status
2. Additional therapies based on comorbidities:
   • Diuretics for symptom relief/congestion
   • Blood pressure control with RAAS antagonists if hypertensive
   • MRAs for poorly controlled hypertension
   • Evidence-based beta blockers if indicated (history of MI, symptomatic CAD, or AF)

Conclusion

For patients with HFpEF, dapagliflozin is the preferred treatment over GLP-1 receptor agonists based on robust evidence demonstrating significant reductions in heart failure hospitalizations, improvements in quality of life, and enhanced exercise capacity. GLP-1 receptor agonists currently lack specific evidence supporting their use in HFpEF management.