What is an alternative to Farxiga (dapagliflozin) for a patient?

Alternative Medications to Farxiga (Dapagliflozin)

Empagliflozin 10-25 mg once daily is the preferred alternative within the same drug class, providing equivalent cardiovascular death reduction, heart failure hospitalization reduction, and renal protection to dapagliflozin. 1

Same Drug Class Alternatives (SGLT2 Inhibitors)

Empagliflozin (First-Line Alternative)

• The European Society of Cardiology recommends empagliflozin and dapagliflozin equally for all types of heart failure (HFrEF, HFmrEF, and HFpEF). 1
• Empagliflozin demonstrates a 25% reduction in cardiovascular death or heart failure hospitalization (HR 0.75,95% CI 0.65-0.86), matching dapagliflozin's efficacy. 1
• Empagliflozin may be particularly advantageous in patients with severely reduced kidney function (eGFR 20-30 mL/min/1.73 m²) based on trial inclusion criteria, though glucose-lowering effects diminish at lower eGFR levels. 1
• Shares similar adverse effect profile with dapagliflozin, including genital mycotic infections, urinary tract infections, and rare risk of euglycemic diabetic ketoacidosis. 2

Canagliflozin (Alternative for Diabetic Kidney Disease)

• Canagliflozin 100-300 mg once daily is particularly effective in patients with diabetic kidney disease, showing a 39% reduction in heart failure hospitalization in the CREDENCE trial. 1
• The American College of Cardiology and European Society of Cardiology recommend canagliflozin equally alongside dapagliflozin and empagliflozin for patients with type 2 diabetes and established cardiovascular disease or very high/high cardiovascular risk. 1

Sotagliflozin (Newer Alternative)

• Sotagliflozin 200 mg once daily demonstrated a 33% reduction in cardiovascular deaths, heart failure hospitalizations, and urgent heart failure visits in the SOLOIST-WHF trial. 1

Different Drug Class Alternative (If SGLT2 Inhibitors Contraindicated)

GLP-1 Receptor Agonists

• The European Society of Cardiology recommends GLP-1 receptor agonists (liraglutide, semaglutide, or dulaglutide) as the alternative drug class when SGLT2 inhibitors cannot be used. 1
• These agents reduce major adverse cardiovascular events (MACE) by 12% and cardiovascular death by 12% in meta-analyses. 1

Key mechanistic difference: GLP-1 receptor agonists primarily reduce atherosclerotic events (myocardial infarction, stroke), while SGLT2 inhibitors primarily reduce heart failure hospitalization and provide more robust renal protection. 1

Clinical Decision Algorithm

For patients with heart failure (any ejection fraction): Choose empagliflozin as the direct substitute. 1

For patients with diabetic kidney disease: Consider canagliflozin for superior renal outcomes. 1

For patients with contraindications to all SGLT2 inhibitors (e.g., recurrent genital infections, history of diabetic ketoacidosis): Switch to GLP-1 receptor agonists, recognizing the shift from heart failure protection to atherosclerotic event reduction. 1

For patients with eGFR 20-30 mL/min/1.73 m²: Empagliflozin may be preferred based on trial data, though cardiovascular benefits persist while glucose-lowering effects are attenuated. 1

Common Pitfalls to Avoid

• Do not assume all SGLT2 inhibitors have identical efficacy profiles—canagliflozin shows particular strength in diabetic kidney disease, while empagliflozin and dapagliflozin have more robust heart failure data across all ejection fraction ranges. 1
• When switching from dapagliflozin to a GLP-1 receptor agonist, counsel patients that the primary benefit shifts from heart failure prevention to atherosclerotic event reduction, which may not be appropriate for all patients. 1
• The combination of SGLT2 inhibitors with GLP-1 receptor agonists provides complementary cardiovascular and renal benefits and should be considered rather than substitution when both drug classes are tolerated. 3