What is the recommended dosing for Xigduo (dapagliflozin and metformin)?

Xigduo Dosing Recommendations

Xigduo (dapagliflozin/metformin combination) should be initiated at dapagliflozin 5 mg/metformin 500-1000 mg once daily in the morning, with titration up to dapagliflozin 10 mg/metformin 2000 mg daily based on glycemic response and tolerability, but is contraindicated when eGFR falls below 45 mL/min/1.73m² for glucose-lowering purposes.

Initial Dosing Strategy

• Start with dapagliflozin 5 mg combined with metformin 500-1000 mg once daily taken in the morning with food to minimize gastrointestinal side effects 1, 2

• The combination can be initiated in treatment-naïve patients or as add-on therapy when metformin monotherapy (≥1500 mg/day) provides inadequate glycemic control 1, 3

• For patients already on metformin, continue their current metformin dose when adding dapagliflozin 1

Dose Titration

• Maximum dose is dapagliflozin 10 mg/metformin 2000 mg daily, which provides superior HbA1c reduction compared to lower doses 2, 3

• Titrate metformin gradually to minimize gastrointestinal adverse effects, typically increasing by 500 mg weekly 2

• Dapagliflozin can be increased from 5 mg to 10 mg after assessing glycemic response, though both doses demonstrate efficacy 1, 2

• The 10 mg dapagliflozin dose achieved mean HbA1c reductions of -0.84% when added to metformin versus -0.30% with placebo 1

Critical Renal Function Considerations

Metformin component adjustments:

• eGFR ≥60 mL/min/1.73m²: No dose adjustment required 4, 5

• eGFR 45-59 mL/min/1.73m²: Continue current metformin dose but monitor renal function every 3-6 months; consider dose reduction in elderly patients or those with liver disease 4, 5

• eGFR 30-44 mL/min/1.73m²: Reduce metformin to half the maximum dose (maximum 1000 mg daily) 4

• eGFR <30 mL/min/1.73m²: Metformin is contraindicated 6, 4

Dapagliflozin component adjustments:

• eGFR ≥45 mL/min/1.73m²: Standard dosing of 5-10 mg daily for glucose lowering 6

• eGFR <45 mL/min/1.73m²: Not recommended for initiation for glucose-lowering purposes 6

• eGFR 25-44 mL/min/1.73m²: May use 10 mg daily for cardiovascular and renal protection (not glucose lowering), but initiation not recommended below eGFR 25 6

• eGFR <25 mL/min/1.73m²: Initiation not recommended; may continue if already established for heart failure or CKD indications 6

• Contraindicated in dialysis patients 6

Monitoring Requirements

• Check renal function at least every 3-6 months when eGFR <60 mL/min/1.73m² to guide dose adjustments 4, 5

• Monitor vitamin B12 levels if metformin therapy exceeds 4 years 4, 5

• Assess glycemic control regularly to determine if dose titration is needed 5

• Implement "sick day rules" to temporarily discontinue during acute illness that may precipitate acute kidney injury 4

Safety Profile and Common Pitfalls

• Genital infections occur in 8-15% of patients on dapagliflozin versus 2-5% on placebo, but rarely require discontinuation 1, 2, 3

• Urinary tract infections occur in 8-13% of dapagliflozin patients versus 4-8% on placebo 2, 3

• Hypoglycemia risk is minimal (2-4%) when used without insulin or sulfonylureas 1, 3

• Critical pitfall: Continuing dapagliflozin for glucose lowering when eGFR drops below 45 mL/min/1.73m² is inappropriate, though continuation may be warranted for cardiovascular/renal protection at lower eGFR ranges 6

Clinical Efficacy

• The combination provides superior HbA1c reduction (-1.98% to -2.05%) compared to either monotherapy alone (dapagliflozin -1.19% to -1.45%, metformin -1.35% to -1.44%) in treatment-naïve patients 2

• Sustained glycemic control is maintained through 102 weeks with mean HbA1c reduction of -0.78% for dapagliflozin 10 mg added to metformin 3

• Additional benefits include weight reduction (1.1-1.7 kg) and fasting plasma glucose reduction (24-37 mg/dL) 1, 3