What is the recommended dosage and use of Dapagliflozin (SGLT2 inhibitor) for type 2 diabetes mellitus and heart failure in adults?

Dapagliflozin Dosage and Uses

Recommended Dosing

For type 2 diabetes mellitus, start dapagliflozin at 5 mg orally once daily, which can be increased to 10 mg daily if additional glycemic control is needed; for heart failure, chronic kidney disease, or cardiovascular risk reduction, use a fixed dose of 10 mg orally once daily. 1, 2

Dosing by Indication

Type 2 Diabetes Mellitus (Glycemic Control):

• Starting dose: 5 mg orally once daily 2
• Maximum dose: 10 mg orally once daily for additional glycemic benefit 2
• Approved for adults and pediatric patients ≥10 years old 2

Heart Failure (with or without reduced ejection fraction):

• Fixed dose: 10 mg orally once daily 1, 2
• No dose titration needed for cardiovascular benefit 1
• Effective regardless of diabetes status 3, 4

Chronic Kidney Disease:

• Fixed dose: 10 mg orally once daily 1, 2
• Reduces risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure 2

Cardiovascular Risk Reduction in Type 2 Diabetes:

• Fixed dose: 10 mg orally once daily 1, 2
• For patients with established cardiovascular disease or multiple cardiovascular risk factors 1, 2

Approved Indications

Dapagliflozin has four distinct FDA-approved indications: 2

1. Chronic kidney disease at risk of progression: Reduces sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure 2

2. Heart failure in adults: Reduces cardiovascular death, hospitalization for heart failure, and urgent heart failure visits (regardless of ejection fraction or diabetes status) 2, 4

3. Type 2 diabetes with cardiovascular disease/risk factors: Reduces hospitalization for heart failure 1, 2

4. Glycemic control: Adjunct to diet and exercise in adults and pediatric patients ≥10 years old with type 2 diabetes 2

Renal Dosing Adjustments

For Glycemic Control (Type 2 Diabetes):

• eGFR ≥45 mL/min/1.73 m²: No dose adjustment needed; use 5-10 mg daily 1, 2
• eGFR <45 mL/min/1.73 m²: NOT recommended for glycemic control (ineffective due to mechanism of action) 1, 2

For Heart Failure or Chronic Kidney Disease Indications:

• eGFR ≥25 mL/min/1.73 m²: Use standard 10 mg daily dose 1, 2
• eGFR <25 mL/min/1.73 m²: Initiation NOT recommended 1, 2
• If eGFR falls below 25 mL/min/1.73 m² during treatment: May continue 10 mg daily 1, 2
• Dialysis: Contraindicated 1, 2

Critical Renal Monitoring Points

An initial eGFR dip of 3-5 mL/min/1.73 m² typically occurs within 1-4 weeks of starting dapagliflozin, which is transient and reversible. 5

• Check eGFR within 1-2 weeks after initiation 5
• This initial decline is hemodynamic and does not indicate kidney injury 5
• Long-term, dapagliflozin slows eGFR decline and reduces risk of kidney failure 1, 2

Contraindications and Critical Precautions

Absolute Contraindications: 2

• History of serious hypersensitivity reaction to dapagliflozin (including anaphylaxis or angioedema) 2

Surgical Precautions:

• Withhold dapagliflozin at least 3 days before major surgery or procedures with prolonged fasting to prevent postoperative ketoacidosis 1, 6, 5, 2
• Resume only when patient is clinically stable and has resumed oral intake 2

Volume Depletion Risk:

• Assess volume status before initiation; correct volume depletion first 2
• Use caution in patients on diuretics, elderly patients, or those with low systolic blood pressure 1, 5
• Consider reducing diuretic dose when starting dapagliflozin 1

Concomitant Glucose-Lowering Therapy:

• If patient is on insulin, consider reducing total daily insulin dose by approximately 20% when starting dapagliflozin to prevent hypoglycemia 1, 6
• If on sulfonylurea or glinide with well-controlled HbA1c, consider weaning or stopping these agents 1

Adverse Effects to Monitor

Common adverse effects include: 1, 5

• Genital mycotic infections (most common) 1, 5
• Urinary tract infections 1
• Volume depletion 1

Rare but serious adverse effects: 1, 5, 2

• Euglycemic diabetic ketoacidosis (can occur even with normal glucose levels; educate patients on symptoms) 1, 5, 2
• Necrotizing fasciitis of the perineum (Fournier gangrene) - requires prompt treatment if suspected 5

Clinical Evidence Supporting Use

Heart Failure Benefits (DAPA-HF Trial):

• In patients with heart failure and reduced ejection fraction, dapagliflozin 10 mg daily reduced the composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85) 4
• Benefits were consistent regardless of diabetes status 3, 4
• First worsening heart failure event reduced by 30% (HR 0.70,95% CI 0.59-0.83) 4
• Cardiovascular death reduced by 18% (HR 0.82,95% CI 0.69-0.98) 4

Chronic Kidney Disease Benefits:

• Reduces risk of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51-0.72) 5
• Slows rate of eGFR decline over time 5
• Benefits observed in patients with eGFR 25-75 mL/min/1.73 m² and albuminuria 1, 5

Limitations of Use

Dapagliflozin is NOT recommended for: 2

• Improving glycemic control in type 1 diabetes mellitus (markedly increases ketoacidosis risk) 2
• Improving glycemic control in type 2 diabetes with eGFR <45 mL/min/1.73 m² (ineffective based on mechanism) 2
• Treating chronic kidney disease in patients with polycystic kidney disease 2
• Treating chronic kidney disease in patients requiring or with recent history of immunosuppressive therapy 2

Common Pitfalls to Avoid

• Do not use dapagliflozin for glycemic control when eGFR <45 mL/min/1.73 m² - it will not effectively lower glucose but can still provide cardiovascular and renal benefits at the 10 mg dose 1, 2
• Do not discontinue dapagliflozin due to initial eGFR dip - a 3-5 mL/min/1.73 m² decline in the first 1-4 weeks is expected and reversible 5
• Do not forget to reduce insulin or sulfonylurea doses when initiating dapagliflozin to prevent hypoglycemia 1, 6
• Do not continue dapagliflozin through surgical procedures - withhold at least 3 days before surgery 1, 6, 5, 2