Is Farxiga (dapagliflozin) indicated in patients with diabetes and nonischemic dilated cardiomyopathy?

Farxiga (Dapagliflozin) for Diabetes and Nonischemic Dilated Cardiomyopathy

Yes, Farxiga (dapagliflozin) is strongly indicated for patients with diabetes and nonischemic dilated cardiomyopathy, as it significantly reduces the risk of worsening heart failure, cardiovascular death, and improves quality of life regardless of diabetes status. 1, 2

Evidence for Farxiga in Heart Failure with Reduced Ejection Fraction

Dapagliflozin has demonstrated substantial benefits in patients with heart failure with reduced ejection fraction (HFrEF), which is commonly seen in nonischemic dilated cardiomyopathy:

• The DAPA-HF trial showed that dapagliflozin 10 mg daily reduced the composite of worsening heart failure or cardiovascular death by 26% (HR 0.74 [95% CI 0.65–0.85]) 1, 3
• Risk of first worsening heart failure event was reduced by 30% (HR 0.70 [95% CI 0.59–0.83]) 3
• Cardiovascular death was reduced by 18% (HR 0.82 [95% CI 0.69–0.98]) 3
• All-cause mortality was reduced by 17% (HR 0.83 [95% CI 0.71–0.97]) 3

Importantly, these benefits were consistent regardless of whether patients had diabetes or not 4. This makes dapagliflozin particularly valuable for patients with both diabetes and heart failure.

Benefits Across Ejection Fraction Spectrum

For patients with nonischemic dilated cardiomyopathy, the benefits of dapagliflozin extend across the ejection fraction spectrum:

• For HFrEF (EF ≤40%): Strong evidence from DAPA-HF showing significant reductions in heart failure hospitalization and cardiovascular death 3
• For HFpEF (EF >40%): The DELIVER trial demonstrated an 18% reduction in the composite of worsening heart failure or cardiovascular death (HR 0.82 [95% CI 0.73–0.92]; P < 0.001) 1

Dosing and Administration

• The recommended dose is 10 mg once daily 2
• No dose adjustment is needed for patients with diabetes, though monitoring for hypoglycemia is recommended if the patient is also on insulin or sulfonylureas 2
• For patients with eGFR 20-30 mL/min/1.73m², Farxiga remains the only SGLT2 inhibitor option 2

Safety Considerations

Dapagliflozin is generally well-tolerated with a favorable safety profile:

• Low inherent risk of hypoglycemia when used as monotherapy 2
• Potential side effects include genital mycotic infections, urinary tract infections, and volume depletion/hypotension 2, 4
• Rare but serious risk of euglycemic diabetic ketoacidosis, particularly in situations of insulin dose reduction, prolonged fasting, or carbohydrate restriction 1
• In the DAPA-HF trial, adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ significantly between dapagliflozin and placebo groups 3

Guideline Recommendations

Current guidelines strongly support the use of SGLT2 inhibitors like dapagliflozin in patients with diabetes and heart failure:

• The American Diabetes Association (2024/2025) recommends SGLT2 inhibitors for patients with type 2 diabetes and established heart failure to reduce the risk of worsening heart failure and cardiovascular death 1
• The European Society of Cardiology (2020) recommends empagliflozin, canagliflozin, or dapagliflozin in patients with T2DM and cardiovascular disease, or at very high/high cardiovascular risk, to reduce cardiovascular events 1
• SGLT2 inhibitors are recommended to improve symptoms, physical limitations, and quality of life in patients with heart failure 1

Clinical Decision Algorithm

1. For patients with diabetes and nonischemic dilated cardiomyopathy with reduced ejection fraction (≤40%):

   • Initiate dapagliflozin 10 mg daily in addition to guideline-directed medical therapy
   • Monitor for volume status and adjust diuretics as needed

2. For patients with diabetes and nonischemic dilated cardiomyopathy with preserved ejection fraction (>40%):

   • Dapagliflozin 10 mg daily is still indicated based on DELIVER trial results
   • Benefits may be somewhat attenuated at very high EFs (>62.5%)

3. For patients with renal impairment:

   • eGFR ≥30 mL/min/1.73m²: Standard dosing of dapagliflozin 10 mg daily
   • eGFR 20-30 mL/min/1.73m²: Dapagliflozin remains an option (unlike other SGLT2 inhibitors)
   • eGFR <20 mL/min/1.73m²: Avoid use

The benefits of dapagliflozin appear to be independent of its glucose-lowering effects, as evidenced by similar outcomes in patients with and without diabetes 1, 4. This makes it particularly valuable in the management of patients with both diabetes and nonischemic dilated cardiomyopathy.