Is Farxiga (dapagliflozin) effective for treating grade 2 diastolic dysfunction?

Dapagliflozin (Farxiga) for Grade 2 Diastolic Dysfunction

Dapagliflozin (Farxiga) is recommended for patients with grade 2 diastolic dysfunction, particularly in those with type 2 diabetes, as it improves diastolic function parameters and reduces heart failure hospitalizations.

Mechanism and Evidence

SGLT2 inhibitors like dapagliflozin have demonstrated significant cardiovascular benefits beyond glycemic control:

• The American College of Cardiology/American Heart Association/Heart Failure Society of America guidelines recommend SGLT2 inhibitors for heart failure patients regardless of diabetes status 1
• Dapagliflozin specifically has shown benefits in both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) 1
• Recent evidence from the LEAVE-DM trial demonstrated that dapagliflozin improves diastolic function parameters in patients with left ventricular dysfunction, including:
  • Reduction in left atrial volume index
  • Improvement in E/e' ratio
  • Enhanced left atrial reservoir strain
  • Improved exercise capacity measured by 6-minute walk distance 2

Clinical Application for Diastolic Dysfunction

For patients with grade 2 diastolic dysfunction:

1. Primary benefit: Dapagliflozin improves diastolic function parameters by:

   • Reducing left atrial volume index by approximately 2.0 ± 9.0 units 2
   • Improving E/e' ratio (a key marker of diastolic function) 2, 3
   • Enhancing left atrial reservoir strain by 1.8 ± 4.0 units 2

2. Secondary benefits:

   • Reduces hospitalization for heart failure by 26-35% 1, 4
   • May slow progression of diastolic dysfunction 5
   • Improves exercise capacity (17 ± 46 m improvement in 6-minute walk distance) 2

Patient Selection and Considerations

Dapagliflozin is particularly beneficial for:

• Patients with type 2 diabetes and diastolic dysfunction 5, 2
• Patients with heart failure regardless of ejection fraction 1
• Patients with chronic kidney disease with or without diabetes 6

Dosing and Monitoring

• Standard dose: 10 mg once daily
• Monitor:
  • Renal function before initiation and periodically during treatment
  • Signs of volume depletion, especially in the first few weeks
  • Risk of genital mycotic infections
  • Rare risk of diabetic ketoacidosis, particularly in patients with type 1 diabetes

Contraindications/Cautions

• eGFR <30 mL/min/1.73m² (dapagliflozin not recommended) 1
• History of severe genital mycotic infections
• Patients at risk for diabetic ketoacidosis
• Pregnancy or breastfeeding

Clinical Pearls

• Dapagliflozin's benefits on diastolic function appear to be independent of its glucose-lowering effects 2
• The European Society of Cardiology and American Diabetes Association recommend SGLT2 inhibitors as first-line agents for patients with diabetes and heart failure 1
• Patients with diabetes duration ≤8 years may experience greater benefits in terms of diastolic dysfunction remission 5
• Benefits extend to patients with preserved ejection fraction, making dapagliflozin particularly valuable for diastolic dysfunction 1, 4

By improving diastolic function parameters, reducing heart failure hospitalizations, and enhancing exercise capacity, dapagliflozin represents an important therapeutic option for patients with grade 2 diastolic dysfunction, especially those with comorbid type 2 diabetes.