What is the recommended usage and dosage of Dapagliflozin (SGLT2 inhibitor) for patients with type 2 diabetes?

Dapagliflozin Dosing and Usage in Type 2 Diabetes

For type 2 diabetes, start dapagliflozin at 5 mg orally once daily for glycemic control, which can be increased to 10 mg once daily if additional glucose lowering is needed; however, use a fixed dose of 10 mg once daily when the primary goal is cardiovascular or renal protection rather than glycemic control. 1, 2, 3

Dosing Algorithm Based on Indication and Renal Function

For Glycemic Control in Type 2 Diabetes

Starting dose: 5 mg orally once daily 1, 2, 3

Titration: May increase to 10 mg once daily if additional glycemic control is needed 1, 2, 3

Renal considerations for glycemic control:

• eGFR ≥45 mL/min/1.73 m²: Use standard dosing (5-10 mg daily) 1, 4, 2
• eGFR <45 mL/min/1.73 m²: Do NOT initiate for glycemic control—dapagliflozin is likely ineffective due to its mechanism of action (requires adequate renal filtration to block glucose reabsorption) 1, 4, 3

For Cardiovascular and Renal Protection

Fixed dose: 10 mg orally once daily for all of the following indications 1, 2, 3:

• Reducing risk of hospitalization for heart failure in patients with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors 1, 2
• Reducing risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in chronic kidney disease 1, 2, 3
• Reducing risk of cardiovascular death and hospitalization for heart failure in heart failure (with or without reduced ejection fraction) 1, 4

Renal considerations for cardiovascular/renal protection:

• eGFR ≥25 mL/min/1.73 m²: Use standard 10 mg daily dose 1, 4, 2
• eGFR <25 mL/min/1.73 m²: Do NOT initiate, but may continue 10 mg daily if already on treatment until dialysis is required 4, 2, 3

Critical distinction: The glucose-lowering efficacy decreases with declining renal function, but cardiovascular and renal protective benefits are preserved at lower eGFR levels down to 25 mL/min/1.73 m² 1, 4

Pre-Initiation Assessment

Before starting dapagliflozin, perform the following 1, 4, 3:

• Check eGFR to determine appropriate dosing and indication 4, 3
• Assess volume status—correct volume depletion before initiating therapy 1, 4, 3
• Consider reducing diuretic dose if patient is on concurrent diuretics to prevent excessive volume depletion 1, 4
• If on insulin: Consider reducing total daily insulin dose by approximately 20% when starting dapagliflozin to prevent hypoglycemia 1, 2
• If on sulfonylurea: Consider weaning or stopping sulfonylurea if HbA1c is well-controlled at baseline or if there is a history of frequent hypoglycemic events 1

Monitoring Requirements

Renal function monitoring: 4

• Check eGFR within 1-2 weeks after initiation 4
• Recheck at least every 3-6 months if eGFR 45-59 mL/min/1.73 m² 4
• Recheck annually if eGFR ≥60 mL/min/1.73 m² 4

Expected initial eGFR dip: A transient, reversible decrease of 3-5 mL/min/1.73 m² typically occurs within the first 1-4 weeks, followed by stabilization and long-term preservation of renal function 4

Critical Safety Precautions and Contraindications

Surgical Procedures

Withhold dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative euglycemic diabetic ketoacidosis 1, 4, 2

Resume only after the patient is clinically stable and has resumed oral intake 2, 3

Sick Day Management

Temporarily discontinue dapagliflozin during acute illness, particularly with 4:

• Fever, vomiting, or diarrhea 4
• Reduced food and fluid intake 4
• Any intercurrent illness requiring hospitalization 4

Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held—complete insulin cessation increases diabetic ketoacidosis risk 4

Resume dapagliflozin only after recovery from acute illness and normal oral intake is re-established 4

Absolute Contraindications

• History of serious hypersensitivity reaction to dapagliflozin (including anaphylaxis and angioedema) 3

Volume Depletion Risk

Use caution in patients with 1, 4:

• Low systolic blood pressure 1, 4
• Concurrent diuretic use 1, 4
• Elderly patients 1, 4
• eGFR 45-59 mL/min/1.73 m² 1

Adverse Effects to Monitor

Common adverse effects (occur more frequently than placebo): 1, 4, 2

• Genital mycotic infections: Occur in approximately 6-9% of patients versus 1-2.5% with placebo 1, 4
• Urinary tract infections: Occur in approximately 9.7% versus 5.1% with placebo 1, 4
• Volume depletion/orthostatic hypotension 1, 4

Rare but serious adverse effects: 1, 4, 2

• Euglycemic diabetic ketoacidosis: Can occur even with normal blood glucose levels—educate patients to check blood or urine ketones if they develop malaise, nausea, or vomiting 1, 4
• Necrotizing fasciitis of the perineum (Fournier gangrene): Requires prompt treatment if suspected 4

Common Pitfalls to Avoid

Do NOT discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m² if the patient is on it for cardiovascular or renal protection—the protective benefits persist even when glycemic efficacy is lost 1, 4

Do NOT use dapagliflozin for glycemic control in patients with eGFR <45 mL/min/1.73 m²—it is ineffective for glucose lowering at this level 1, 4, 3

Do NOT reduce insulin doses excessively when holding dapagliflozin during illness—this combination significantly elevates ketoacidosis risk 4

Evidence Supporting Cardiovascular and Renal Benefits

The DAPA-CKD trial demonstrated that dapagliflozin 10 mg daily in patients with chronic kidney disease (eGFR 25-75 mL/min/1.73 m²) and albuminuria reduced 4, 2:

• Primary composite outcome (≥50% sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death) by 39% (HR 0.61,95% CI 0.51-0.72) 4, 2
• Renal composite outcome by 44% (HR 0.56,95% CI 0.45-0.68) 4, 2
• Cardiovascular death or hospitalization for heart failure by 29% (HR 0.71,95% CI 0.55-0.92) 4, 2

These benefits were consistent in patients both with and without type 2 diabetes 4