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

Alternative Medications to Farxiga (Dapagliflozin)

Empagliflozin is the primary alternative to dapagliflozin, as both SGLT2 inhibitors demonstrate equivalent cardiovascular and heart failure benefits with similar safety profiles. 1

SGLT2 Inhibitor Alternatives (Same Drug Class)

The most direct alternatives are other SGLT2 inhibitors, which share the same mechanism of action and clinical benefits:

Empagliflozin (First-Line Alternative)

• Empagliflozin 10-25 mg once daily provides equivalent cardiovascular death reduction, heart failure hospitalization reduction, and renal protection compared to dapagliflozin. 1
• The EMPEROR-Reduced trial demonstrated a 25% reduction in cardiovascular death or heart failure hospitalization (HR 0.75,95% CI 0.65-0.86), nearly identical to dapagliflozin's 26% reduction in DAPA-HF. 1
• Both drugs are recommended equally by the European Society of Cardiology for heart failure with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF). 1
• Empagliflozin demonstrated a 35% reduction in heart failure hospitalization in the EMPA-REG OUTCOME trial and showed mortality benefit in patients with established cardiovascular disease. 1

Canagliflozin (Second-Line Alternative)

• 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 CANVAS program demonstrated a 33% reduction in heart failure hospitalization, consistent with other SGLT2 inhibitors. 1
• Canagliflozin provides robust renal protection with a 30% reduction in composite cardio-renal endpoints in patients with chronic kidney disease and albuminuria (UACR 300-5,000 mg/g). 1

Sotagliflozin (Dual SGLT1/SGLT2 Inhibitor)

• Sotagliflozin 200 mg once daily showed a 33% reduction in cardiovascular deaths, heart failure hospitalizations, and urgent heart failure visits in the SOLOIST-WHF trial. 1
• This agent may be considered when both SGLT1 and SGLT2 inhibition is desired, though it carries higher rates of diarrhea (6.1% vs 3.4%) and severe hypoglycemia (1.5% vs 0.3%) compared to placebo. 1

Key Clinical Considerations for SGLT2 Inhibitor Selection

Renal Function Thresholds

• DAPA-HF excluded patients with eGFR <30 mL/min/1.73 m², while EMPEROR-Reduced included patients down to eGFR 20 mL/min/1.73 m². 1
• Empagliflozin may be preferred in patients with eGFR 20-30 mL/min/1.73 m² based on trial inclusion criteria, though glucose-lowering effects are attenuated at lower eGFR levels. 1

Cardiovascular Disease Context

• All three major SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin) are recommended equally for patients with type 2 diabetes and established cardiovascular disease or very high/high cardiovascular risk. 1
• Empagliflozin specifically demonstrated mortality reduction in patients with established cardiovascular disease in EMPA-REG OUTCOME. 1, 2

Heart Failure Phenotype

• Both dapagliflozin and empagliflozin are Class I recommendations for HFrEF, HFmrEF, and HFpEF regardless of diabetes status. 1
• The PRESERVED-HF trial showed dapagliflozin improves symptoms and exercise function in HFpEF patients, suggesting class effect benefits extend across ejection fraction spectrum. 1

Alternative Drug Classes (If SGLT2 Inhibitors Contraindicated)

GLP-1 Receptor Agonists

If SGLT2 inhibitors cannot be used (e.g., recurrent genital infections, diabetic ketoacidosis risk), GLP-1 receptor agonists provide cardiovascular benefit through different mechanisms:

• Liraglutide, semaglutide, or dulaglutide reduce major adverse cardiovascular events (MACE) by 12% and cardiovascular death by 12% in meta-analyses. 1
• These agents reduce stroke risk by 16% and provide renal protection primarily through albuminuria reduction. 1
• Liraglutide specifically demonstrated all-cause mortality reduction in the LEADER trial. 1

Important Distinction

• GLP-1 receptor agonists primarily reduce atherosclerotic events (MI, stroke), while SGLT2 inhibitors primarily reduce heart failure hospitalization and provide more robust renal protection. 1
• The mechanisms are complementary rather than equivalent, so the choice depends on the patient's predominant risk profile (atherosclerotic vs. heart failure).

Common Pitfalls to Avoid

• Do not assume all SGLT2 inhibitors require discontinuation at the same eGFR threshold—empagliflozin has data down to eGFR 20 mL/min/1.73 m², while dapagliflozin trials excluded patients below 30 mL/min/1.73 m². 1
• Discontinue any SGLT2 inhibitor at least 3 days before planned surgery to prevent postoperative diabetic ketoacidosis. 3
• Monitor volume status before initiation and consider reducing diuretic doses in patients at risk for volume depletion, as all SGLT2 inhibitors cause osmotic diuresis. 1, 3
• The cardiovascular and renal benefits of SGLT2 inhibitors are independent of glucose-lowering effects, so they should be continued even if glucose control is adequate with other agents. 1, 3