What is the recommended treatment regimen for an adult patient with type 2 diabetes or heart failure, considering the use of Farxiga (dapagliflozin)?

Farxiga (Dapagliflozin) Treatment Regimen

For adults with type 2 diabetes, heart failure, or chronic kidney disease, dapagliflozin 10 mg once daily is the standard fixed dose for all indications, providing cardiovascular and renal protection independent of glycemic control needs. 1, 2

Dosing by Indication

Type 2 Diabetes with Cardiovascular/Renal Risk

• Initiate dapagliflozin 10 mg once daily if eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection, regardless of baseline HbA1c or need for additional glucose lowering 1, 2
• For glycemic control specifically, start 5 mg once daily if eGFR ≥45 mL/min/1.73 m², with option to increase to 10 mg if additional glycemic control needed 2, 3
• Do not initiate for glycemic control if eGFR <45 mL/min/1.73 m², as glucose-lowering efficacy is significantly reduced, though cardiovascular/renal benefits persist 1, 2

Heart Failure (HFrEF or HFpEF)

• Dapagliflozin 10 mg once daily is recommended for all patients with NYHA class II-IV heart failure and ejection fraction ≤40%, with or without diabetes 1
• Reduces cardiovascular death or heart failure hospitalization by 26% (HR 0.74,95% CI 0.65-0.85) 1, 4
• Reduces heart failure hospitalization by 30% and urgent heart failure visits by 57% 5
• No dose titration required or recommended—10 mg daily is the universal dose across all heart failure types 2

Chronic Kidney Disease

• Initiate 10 mg once daily if eGFR ≥25 mL/min/1.73 m² and UACR ≥200 mg/g, regardless of diabetes status 1, 2
• Reduces primary composite renal endpoint (≥50% sustained eGFR decline, ESKD, or renal/CV death) by 39% (HR 0.61,95% CI 0.51-0.72) 1, 2
• Reduces kidney-specific composite by 44% (HR 0.56,95% CI 0.45-0.68) 1, 2
• If eGFR falls below 25 mL/min/1.73 m² during treatment, continue 10 mg daily until dialysis is required 2

Critical Renal Function Thresholds

eGFR ≥45 mL/min/1.73 m²:

• Full glycemic efficacy maintained 2
• No dose adjustment needed for any indication 2

eGFR 25-44 mL/min/1.73 m²:

• Cardiovascular and renal protective benefits fully preserved 2, 6
• Glycemic efficacy significantly reduced but 10 mg daily remains appropriate for CV/renal protection 2
• Do not discontinue solely because eGFR falls below 45 mL/min/1.73 m² 2

eGFR <25 mL/min/1.73 m²:

• Do not initiate new therapy 2
• If already on treatment, may continue 10 mg daily for CV/renal protection until dialysis 2

Combination Therapy Considerations

With Metformin

• Continue metformin without adjustment if eGFR ≥60 mL/min/1.73 m² 2
• Reduce metformin to half maximum dose if eGFR 45-59 mL/min/1.73 m², or maximum 1000 mg/day if eGFR 30-44 mL/min/1.73 m² 2
• Stop metformin if eGFR <30 mL/min/1.73 m², but continue dapagliflozin for CV/renal protection 2

With Sulfonylureas

• Consider stopping gliclazide or other sulfonylureas when starting dapagliflozin, as combination increases hypoglycemia risk without additional cardiovascular benefit 2
• If continuing sulfonylurea, adjust dose based on glucose monitoring 2

With Insulin

• Reduce total daily insulin dose by approximately 20% when initiating dapagliflozin if HbA1c is well-controlled at baseline 7
• Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held during illness 2

Safety Precautions and Monitoring

Before Initiation

• Check eGFR and assess volume status 2, 6
• Correct volume depletion if present, particularly in elderly patients or those on concurrent diuretics 2, 6
• Consider reducing concurrent diuretic doses to prevent excessive volume depletion 2

Sick Day Management

• Withhold dapagliflozin during acute illness, particularly with reduced oral intake, fever, vomiting, or diarrhea 2
• Monitor for euglycemic diabetic ketoacidosis even with normal blood glucose levels 2
• Check blood or urine ketones if patients develop malaise, nausea, or vomiting 2
• Resume only after recovery and normal oral intake re-established 2

Surgical Procedures

• Withhold at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis 2, 6

Ongoing Monitoring

• Recheck eGFR within 1-2 weeks after initiation (expect transient 3-5 mL/min/1.73 m² dip) 2, 6
• Monitor eGFR at least every 3-6 months if eGFR 45-59 mL/min/1.73 m², or annually if ≥60 mL/min/1.73 m² 2
• Assess for genital mycotic infections (occur in ~6% vs 1% placebo) 2, 6

Common Pitfalls to Avoid

Do not reduce or discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 2

Do not withhold ACE inhibitors/ARBs when starting dapagliflozin—these should be continued for synergistic renal protection 2

Do not completely stop insulin when holding dapagliflozin during illness—this combination significantly elevates ketoacidosis risk 2

Do not use dapagliflozin for glycemic control as monotherapy in advanced CKD (eGFR <30 mL/min/1.73 m²)—consider GLP-1 receptor agonists or insulin instead 1, 2

Cardiovascular Outcomes Evidence

The DECLARE-TIMI 58 trial demonstrated that dapagliflozin reduced cardiovascular death or heart failure hospitalization by 17% (HR 0.83,95% CI 0.73-0.95) in a broad population of patients with type 2 diabetes 1, 8. The DAPA-HF trial showed benefits independent of diabetes status, with similar efficacy in patients with and without diabetes (P for interaction = 0.80) 4. In patients with HFrEF specifically, dapagliflozin reduced the primary outcome by 38% (HR 0.62,95% CI 0.45-0.86) 9.

Renal benefits from the DAPA-CKD trial were consistent across patients with and without diabetes, with 67.5% having diabetes and 32.5% without diabetes showing similar treatment effects 2.