Farxiga (Dapagliflozin): Indications and Usage
Farxiga is FDA-approved for three distinct indications: (1) improving glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise, (2) reducing the risk of cardiovascular death and hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, and (3) reducing the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure with reduced ejection fraction (HFrEF), regardless of diabetes status. 1
Primary Indications
Type 2 Diabetes Management
- Dapagliflozin 10 mg daily is indicated to improve glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise 1
- The medication lowers blood glucose independent of insulin secretion by inhibiting renal glucose reabsorption, promoting urinary glucose excretion 2
- Treatment is associated with weight reduction and has a low intrinsic propensity to cause hypoglycemia 2
Cardiovascular Risk Reduction in Type 2 Diabetes
- Dapagliflozin reduces the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors 1
- In the DECLARE-TIMI 58 trial, dapagliflozin demonstrated a 27% reduction in hospitalization for heart failure versus placebo 1
- The cardiovascular benefits remain consistent regardless of background use of ACE inhibitors/ARBs, beta-blockers, diuretics, or mineralocorticoid receptor antagonists 3
Heart Failure with Reduced Ejection Fraction
- Dapagliflozin 10 mg daily is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with HFrEF (NYHA class II-IV, ejection fraction ≤40%), regardless of diabetes status 1, 4
- In the DAPA-HF trial involving 4,744 patients (45% with type 2 diabetes), dapagliflozin reduced the primary composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85) 1, 4
- Specific benefits included a 30% reduction in first worsening heart failure event (HR 0.70,95% CI 0.59-0.83) and an 18% reduction in cardiovascular death (HR 0.82,95% CI 0.69-0.98) 1
- The effect was consistent regardless of the presence or absence of type 2 diabetes 1
Dosing and Modifications
Standard Dosing
- The recommended dose is 10 mg orally once daily for all approved indications 1
Renal Function Considerations
- For glycemic control: Use is not recommended when eGFR <45 mL/min/1.73 m² and is contraindicated when eGFR <30 mL/min/1.73 m² 1
- For heart failure indication: The benefits in HFrEF have been demonstrated across a range of renal function, though caution is warranted with severe renal impairment 4
Contraindications and Key Cautions
Absolute Contraindications
- History of serious hypersensitivity reaction to dapagliflozin 1
- End-stage renal disease (ESRD) 1
- Patients on dialysis 1
Critical Safety Considerations
- Discontinue at least 3 days before planned surgery to prevent postoperative ketoacidosis 1
- Monitor for euglycemic ketoacidosis, particularly in patients with type 1 diabetes (though not an approved indication), insulin pump users, or those with significant insulin dose reductions 1
- Increased risk of genital infections, urinary tract infections, and rarely Fournier's gangrene 5
- Monitor for volume depletion, especially when combined with diuretics 4
Clinical Context and Evidence Quality
The evidence supporting dapagliflozin's use spans multiple high-quality randomized controlled trials. The DAPA-HF trial represents the most robust evidence for heart failure benefits, demonstrating consistent effects across diabetes status 1, 6. The DECLARE-TIMI 58 trial established cardiovascular benefits in the type 2 diabetes population with or at risk for atherosclerotic cardiovascular disease 6, 3.
The 2025 American Diabetes Association guidelines strongly recommend SGLT2 inhibitors with proven benefit (including dapagliflozin) for patients with type 2 diabetes and established HFrEF to reduce the risk of worsening heart failure and cardiovascular death 1. The American College of Cardiology similarly recommends SGLT2 inhibitors for all patients with symptomatic heart failure regardless of ejection fraction or diabetes status 4.
The benefits of dapagliflozin appear independent of its glucose-lowering effects, representing direct cardiovascular and renal protective mechanisms 4, 5.