What are the approved and off‑label uses of Farxiga (dapagliflozin) and the recommended dosing for each indication?

Approved and Off-Label Uses of Farxiga (Dapagliflozin)

Farxiga (dapagliflozin) is FDA-approved for four distinct indications: chronic kidney disease at risk of progression, heart failure (regardless of ejection fraction), type 2 diabetes with cardiovascular risk factors, and glycemic control in type 2 diabetes—each with a specific dosing regimen based on the indication and renal function. 1

FDA-Approved Indications and Dosing

1. Chronic Kidney Disease (CKD) at Risk of Progression

• Indication: To reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with CKD at risk of progression. 1

• Dosing: 10 mg orally once daily when eGFR ≥25 mL/min/1.73 m². 1

• Initiation threshold: Do not initiate if eGFR <25 mL/min/1.73 m², but if eGFR falls below 25 mL/min/1.73 m² during treatment, continue 10 mg daily until dialysis. 2, 1

• Evidence base: The DAPA-CKD trial demonstrated a 44% reduction in kidney-specific outcomes (sustained eGFR decline ≥50%, end-stage kidney disease, or renal death) and a 39% reduction in the composite of sustained eGFR decline, end-stage kidney disease, or cardiovascular/renal death. 2

• Key eligibility: Most robust benefit when UACR ≥200 mg/g, though approved for broader CKD at risk of progression. 2

• Important note: Benefits occur regardless of diabetes status—67.5% of DAPA-CKD participants had type 2 diabetes and 32.5% did not, with consistent effects in both groups. 2

2. Heart Failure (All Ejection Fraction Categories)

• Indication: To reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure. 1

• Dosing: 10 mg orally once daily, regardless of ejection fraction or diabetes status. 2, 3

• Renal threshold: Can be initiated when eGFR ≥25 mL/min/1.73 m². 2, 1

• Evidence base:

  • HFrEF (≤40%): DAPA-HF trial showed 26% reduction in cardiovascular death or worsening heart failure. 2, 4
  • HFpEF (≥50%): DELIVER trial demonstrated 18% reduction in worsening heart failure or cardiovascular death. 2
  • Mildly reduced EF (41-49%): Same 10 mg dose applies across the entire heart failure spectrum. 2

3. Type 2 Diabetes with Cardiovascular Risk

• Indication: To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes and either established cardiovascular disease or multiple cardiovascular risk factors. 1

• Dosing: 10 mg orally once daily. 3, 5

• Risk factor criteria: Age ≥55 years (men) or ≥60 years (women) with at least one additional risk factor: dyslipidemia, hypertension, tobacco use, coronary/carotid/lower extremity stenosis >50%, left ventricular hypertrophy, eGFR <60 mL/min/1.73 m², or albuminuria. 3

• Evidence base: DECLARE-TIMI 58 trial showed 27% reduction in hospitalization for heart failure and 17% reduction in cardiovascular death or heart failure hospitalization. 3, 6

4. Glycemic Control in Type 2 Diabetes

• Indication: As adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged ≥10 years with type 2 diabetes. 1

• Dosing:

  • Starting dose: 5 mg orally once daily. 1
  • Titration: May increase to 10 mg once daily for additional glycemic control. 1

• Renal limitations for glycemic indication:

  • eGFR ≥45 mL/min/1.73 m²: No dose adjustment required. 2, 1
  • eGFR <45 mL/min/1.73 m²: Not recommended for glycemic control (likely ineffective due to mechanism of action), though 10 mg may be continued for cardiovascular/renal protection. 2, 1

• Pediatric use: Approved for patients aged ≥10 years for glycemic control only. 1

Critical Dosing Distinctions by Indication

Indication	Dose	Minimum eGFR for Initiation	Continue if eGFR Falls Below Threshold?
Glycemic control	5–10 mg daily	≥45 mL/min/1.73 m²	No—ineffective for glucose lowering [2]
CKD protection	10 mg daily	≥25 mL/min/1.73 m² (some guidelines ≥20)	Yes—continue until dialysis [2,1]
Heart failure	10 mg daily	≥25 mL/min/1.73 m²	Yes—continue until dialysis [2,1]
CV risk reduction in T2DM	10 mg daily	≥25 mL/min/1.73 m²	Yes—CV benefits persist [2]

Limitations of Use (FDA-Specified)

• Type 1 diabetes: Not recommended—significantly increases risk of diabetic ketoacidosis. 1

• Polycystic kidney disease: Not recommended—not expected to be effective. 1

• Immunosuppressive therapy for kidney disease: Not recommended—insufficient evidence. 1

• eGFR <25 mL/min/1.73 m² (new initiation): Not recommended, though continuation is acceptable if already on therapy. 1

Off-Label Uses (Not FDA-Approved but Supported by Guidelines)

1. Primary Prevention of Heart Failure in Type 2 Diabetes

• Dapagliflozin reduces incident heart failure hospitalization by 17% in patients with type 2 diabetes without prior heart failure, demonstrating clear benefit in primary prevention. 2

• The 2024 American Diabetes Association guidelines emphasize initiating SGLT2 inhibitors in patients with type 2 diabetes and increased cardiovascular risk to prevent the development of incident heart failure. 2

2. CKD Without Albuminuria

• While strongest evidence exists for UACR ≥200 mg/g, dapagliflozin is approved for "CKD at risk of progression" more broadly, and guidelines support use when eGFR is declining even without significant albuminuria. 2, 1

3. Cardiorenal Protection Independent of Glycemic Control

• Guidelines explicitly recommend dapagliflozin for cardiovascular and renal protection irrespective of the need for additional glucose lowering and irrespective of metformin use. 2

• Benefits occur independently of baseline HbA1c levels, including patients with HbA1c <7%. 3

Pre-Initiation Requirements

• Assess renal function (eGFR) prior to initiation and periodically thereafter. 2, 1

• Evaluate volume status and correct any depletion before starting; consider reducing concurrent diuretic doses in high-risk patients. 2, 1

• Exclude acute kidney injury by reviewing creatinine trends and ruling out prerenal, intrinsic, or post-renal causes. 2

Safety Precautions and Monitoring

• Withhold at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 2, 1

• Temporarily discontinue during acute illness with reduced oral intake, fever, vomiting, or diarrhea. 2

• Expected eGFR dip: A reversible decline of 2–5 mL/min/1.73 m² within the first 2–4 weeks is hemodynamic and should not prompt discontinuation. 2

• Genital mycotic infections occur in approximately 6% of patients versus 1% with placebo; emphasize daily hygiene. 2

• Euglycemic diabetic ketoacidosis is rare but serious—warn patients to seek immediate care for malaise, nausea, vomiting, or abdominal pain even when blood glucose is normal. 2, 1

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal benefits persist despite loss of glycemic efficacy. 2

• Do not stop the drug because of the expected initial eGFR dip in the first 2–4 weeks. 2

• Do not reduce the dose below 10 mg for cardiovascular or renal indications, even if glycemic efficacy wanes at lower eGFR—all outcome trials used the fixed 10 mg dose. 2

• Do not withhold ACE inhibitors or ARBs when starting dapagliflozin—more than 99% of DAPA-CKD participants were on renin-angiotensin-aldosterone system blockers, and the combination showed additive renal protection. 2

Integration with Other Therapies

• Continue metformin if eGFR ≥60 mL/min/1.73 m² without adjustment; reduce to ≤1000 mg/day if eGFR 30–44 mL/min/1.73 m². 2

• Reduce insulin dose by approximately 20% when baseline HbA1c is <8.5% to mitigate hypoglycemia risk. 2

• Discontinue sulfonylureas when baseline HbA1c is <8.5%—the combination increases hypoglycemia risk without cardiovascular benefit. 2

• Consider reducing loop diuretic doses, especially in elderly patients, to avoid excessive volume depletion. 2