What is the recommended use and dosage of Dapagliflozin (Forxiga) for patients with type 2 diabetes or heart failure?

Dapagliflozin: Recommended Use and Dosing

Dapagliflozin 10 mg once daily is recommended for adults with heart failure (regardless of ejection fraction or diabetes status), chronic kidney disease at risk of progression, or type 2 diabetes with established cardiovascular disease or multiple risk factors, with proven benefits in reducing cardiovascular death, heart failure hospitalizations, and disease progression. 1

FDA-Approved Indications

Dapagliflozin is approved for four distinct clinical scenarios 1:

• Chronic kidney disease at risk of progression: Reduces sustained eGFR decline, end-stage kidney disease, cardiovascular death, and heart failure hospitalization 1
• Heart failure (any ejection fraction): Reduces cardiovascular death, heart failure hospitalization, and urgent heart failure visits in adults with heart failure 1
• Type 2 diabetes with cardiovascular risk: Reduces heart failure hospitalization in patients with established cardiovascular disease or multiple cardiovascular risk factors 1
• Glycemic control: Adjunct to diet and exercise in adults and pediatric patients ≥10 years with type 2 diabetes 1

Dosing Recommendations

For Heart Failure, Chronic Kidney Disease, and Cardiovascular Risk Reduction

The standard dose is dapagliflozin 10 mg orally once daily 2, 1:

• Initiate at 10 mg daily for all non-glycemic indications 1
• Can be started in patients with eGFR ≥25 mL/min/1.73 m² 1
• If eGFR falls below 25 mL/min/1.73 m² during treatment, continue dapagliflozin 10 mg daily 1
• Do NOT initiate if eGFR <25 mL/min/1.73 m² 1

For Glycemic Control in Type 2 Diabetes

Start with 5 mg once daily, increase to 10 mg daily if additional glycemic control is needed 1:

• Initial dose: 5 mg orally once daily 1
• Maximum dose: 10 mg orally once daily 1
• Not recommended for glycemic control if eGFR <45 mL/min/1.73 m² (ineffective due to mechanism of action) 1
• Contraindicated if eGFR <30 mL/min/1.73 m² 2, 1

Evidence for Cardiovascular and Heart Failure Benefits

Heart Failure with Reduced Ejection Fraction (HFrEF)

Dapagliflozin demonstrated a 26% reduction in the composite outcome of worsening heart failure or cardiovascular death in the DAPA-HF trial 2:

• The DAPA-HF trial enrolled 4,744 patients with HFrEF (EF ≤40%), NYHA class II-IV 3, 4
• Primary outcome (worsening HF or CV death): HR 0.74 (95% CI 0.65-0.85) 2, 3
• First worsening heart failure event: HR 0.70 (95% CI 0.59-0.83) 3
• Cardiovascular death: HR 0.82 (95% CI 0.69-0.98) 3
• Benefits were consistent regardless of diabetes status 3

Heart Failure with Preserved or Mildly Reduced Ejection Fraction

The DELIVER trial demonstrated an 18% reduction in worsening heart failure or cardiovascular death in patients with EF >40% 5:

• Enrolled 6,263 patients with heart failure and EF >40% 5, 6
• Primary outcome: HR 0.82 (95% CI 0.73-0.92, P <0.001) 5
• Benefits were consistent across normoglycemia, prediabetes, and type 2 diabetes subgroups 6

Type 2 Diabetes with Cardiovascular Risk

In the DECLARE-TIMI 58 trial, dapagliflozin reduced the composite of cardiovascular death or heart failure hospitalization by 17% 2:

• HR 0.83 (95% CI 0.73-0.95) for CV death or heart failure hospitalization 2
• The trial enrolled 59.4% of participants without prior established CVD but with multiple risk factors 2
• Demonstrated cardiovascular safety but not MACE benefit (HR 0.93,95% CI 0.84-1.03) 2

Key Clinical Considerations

Pre-Treatment Assessment

Assess renal function and volume status before initiating dapagliflozin 1:

• Check eGFR to determine appropriate indication and dosing 1
• Correct volume depletion before starting therapy 1
• Consider reducing or stopping diuretics if volume depletion is a concern 2

Diabetes Management Adjustments

If HbA1c is well-controlled or patient has frequent hypoglycemia, reduce concomitant glucose-lowering medications 2:

• Wean or stop sulfonylurea or glinide 2
• Consider reducing total daily insulin dose by approximately 20% 2

Surgical Considerations

Withhold dapagliflozin for at least 3 days before major surgery or procedures with prolonged fasting 2, 1:

• This prevents postoperative ketoacidosis 2
• Resume when patient is clinically stable and has resumed oral intake 1

Contraindications and Important Cautions

Absolute Contraindications

• History of serious hypersensitivity reaction to dapagliflozin (including anaphylaxis and angioedema) 1
• Pregnancy or breastfeeding 2
• End-stage renal disease (ESRD) 2
• eGFR <30 mL/min/1.73 m² (for glycemic control indication) 2, 1

Safety Monitoring

Monitor for genital fungal infections, urinary tract infections, and euglycemic diabetic ketoacidosis 2:

• Genital fungal infections are common adverse effects 2
• Euglycemic ketoacidosis can occur even with normal glucose levels 2
• Volume depletion risk, especially when combined with diuretics 2

Special Populations Requiring Caution

Use with caution in patients with prior amputation, severe peripheral neuropathy, severe peripheral vascular disease, or active diabetic foot ulcers 2:

• These patients may have increased risk of lower limb complications 2

Benefits Independent of Glycemic Control

The cardiovascular and heart failure benefits of dapagliflozin appear independent of glucose-lowering effects 2, 5:

• Benefits observed across the entire HbA1c spectrum 2, 6
• DAPA-HF demonstrated equal benefit in patients with and without diabetes 3
• Treatment decisions for cardiovascular/heart failure indications should be made independently of baseline HbA1c 2