What are the alternatives to Farxiga (dapagliflozin)?

Alternatives to Farxiga (Dapagliflozin)

For patients requiring an SGLT2 inhibitor, empagliflozin and canagliflozin are the primary alternatives to dapagliflozin (Farxiga), with similar efficacy profiles for cardiovascular and renal outcomes. 1

SGLT2 Inhibitor Alternatives

Direct SGLT2 Inhibitor Substitutes

• Empagliflozin (Jardiance)

  • Similar cardiovascular benefits to dapagliflozin
  • Recommended for reducing CV death in patients with T2D and CVD 1
  • Effective for heart failure with reduced ejection fraction (HFrEF) 1
  • Can be initiated at eGFR ≥20 mL/min/1.73m² 1

• Canagliflozin (Invokana)

  • Effective for reducing MACE, heart failure hospitalization, and renal outcomes 1
  • Particularly strong evidence in diabetic nephropathy with albuminuria 1
  • Caution: Higher risk of lower limb amputations compared to other SGLT2 inhibitors 1

Dosing Considerations

• All SGLT2 inhibitors should be initiated at the lowest dose tested in CV outcome trials 1
• Empagliflozin: 10 mg PO daily
• Canagliflozin: 100 mg PO daily
• Dapagliflozin: 10 mg PO daily

Alternative Drug Classes

GLP-1 Receptor Agonists

For patients who need cardiovascular protection but cannot take SGLT2 inhibitors:

• Liraglutide, semaglutide, or dulaglutide
  • Recommended for T2D patients with CVD or high CV risk 1
  • Reduce cardiovascular events but with neutral effect on heart failure 1
  • Better for weight loss than SGLT2 inhibitors 1
  • Main side effects: nausea, vomiting, diarrhea 1

DPP-4 Inhibitors

For patients needing a weight-neutral alternative with low hypoglycemia risk:

• Sitagliptin or linagliptin
  • Neutral effect on heart failure 1
  • Lower glucose-lowering efficacy than SGLT2 inhibitors 1
  • Avoid saxagliptin in patients with heart failure risk 1

Metformin

• First-line therapy for most T2D patients
• Can be used with eGFR >30 mL/min/1.73m² 1
• Consider in patients with diabetes and heart failure if eGFR >30 mL/min/1.73m² 1

Clinical Decision Algorithm

1. If patient needs cardiovascular protection:

   • For patients with established atherosclerotic CVD: Empagliflozin (preferred for CV death reduction) or canagliflozin 1
   • For patients with heart failure: Empagliflozin or dapagliflozin (both have HF indication) 1
   • For patients with CKD: Canagliflozin (strongest evidence in diabetic nephropathy) 1

2. If patient cannot tolerate SGLT2 inhibitors:

   • For CV protection: GLP-1 RA (liraglutide, semaglutide, dulaglutide) 1
   • For general glucose control: DPP-4 inhibitors (except saxagliptin) or metformin 1

3. If renal function is impaired:

   • eGFR 30-45 mL/min/1.73m²: All SGLT2 inhibitors can be used (minimal glucose-lowering effect but CV/renal benefits persist) 1
   • eGFR 20-30 mL/min/1.73m²: Empagliflozin or dapagliflozin (for CV/renal benefits only) 1
   • eGFR <20 mL/min/1.73m²: Avoid all SGLT2 inhibitors 1

Important Monitoring Considerations

All SGLT2 inhibitors share similar adverse effect profiles requiring monitoring for:

• Genital mycotic infections (counsel on genital hygiene) 1
• Volume depletion (consider reducing diuretic doses) 1
• Diabetic ketoacidosis risk (educate on sick day management) 1
• Hypoglycemia when used with insulin or sulfonylureas 1

Common Pitfalls to Avoid

• Do not discontinue SGLT2 inhibitors if eGFR falls below initiation threshold (unless not tolerated or KRT initiated) 1
• Do not forget to hold SGLT2 inhibitors during acute illness or 3-4 days before surgery 1
• Do not use SGLT2 inhibitors in patients with type 1 diabetes due to DKA risk 1
• Do not use pioglitazone in patients with heart failure as an alternative 1

The choice between SGLT2 inhibitor alternatives should be based on the specific comorbidities, with empagliflozin having the strongest evidence for CV death reduction and canagliflozin for diabetic nephropathy with albuminuria.