What is the appropriate dosage of Xigduo (dapagliflozin and metformin) for a patient with poorly controlled type 2 diabetes and an elevated Hemoglobin A1C (HbA1C) level?

Xigduo Dosing for A1C 10.0%

For a patient with poorly controlled type 2 diabetes (A1C 10.0%), start Xigduo XR 5 mg dapagliflozin/1000 mg metformin twice daily, then increase to 10 mg dapagliflozin/1000 mg metformin twice daily after tolerability is established if additional glycemic control is needed. 1

Initial Assessment Required

Before starting Xigduo, you must:

• Assess renal function (eGFR must be ≥45 mL/min/1.73 m² for glycemic control indication) 1
• Evaluate volume status and correct any volume depletion before initiation 1
• Screen for cardiovascular disease to determine if the patient qualifies for cardiovascular risk reduction benefits 2

Dosing Algorithm

Starting Dose

• Begin with Xigduo XR 5 mg/1000 mg twice daily (total daily: dapagliflozin 10 mg + metformin 2000 mg) 1
• This provides the FDA-approved starting dose of dapagliflozin (5 mg once daily equivalent when given as combination) plus maximum metformin dose 1

Dose Escalation

• If A1C remains ≥7% after 3 months, increase to Xigduo XR 10 mg/1000 mg twice daily (total daily: dapagliflozin 20 mg + metformin 2000 mg) for additional glycemic control 1
• The maximum approved dose is dapagliflozin 10 mg once daily for glycemic control, but combination products may deliver this differently 1

Expected Efficacy at Baseline A1C 10.0%

With an A1C of 10.0%, combination dapagliflozin plus metformin demonstrates robust efficacy:

• Expected A1C reduction of approximately 2.0% when starting both agents together in treatment-naïve patients with baseline A1C 7.5-12% 3
• Dapagliflozin alone reduces A1C by 0.55-0.90% when added to existing therapy 4
• Additional benefits include weight loss of 1.3-2.0 kg and fasting plasma glucose reduction of 16-31 mg/dL 4, 5

Renal Function Considerations

Critical dosing adjustments based on eGFR:

• eGFR ≥45 mL/min/1.73 m²: Use standard dosing as above for glycemic control 1
• eGFR 25-44 mL/min/1.73 m²: Dapagliflozin is NOT recommended for glycemic control (ineffective due to mechanism of action), but may be continued at 10 mg daily for cardiovascular/renal protection if already established 1
• eGFR <25 mL/min/1.73 m²: Do not initiate; may continue if already on therapy for non-glycemic benefits 1

Monitoring Requirements

Follow-up schedule:

• Reassess A1C every 3 months until target achieved 2
• Monitor renal function periodically, especially if eGFR approaches 45 mL/min/1.73 m² 1
• Check for genital mycotic infections (occurs in 11.7-14.6% of patients) and urinary tract infections (8.0-13.3%) 5
• Monitor for signs of ketoacidosis (nausea, vomiting, abdominal pain, weakness), though rare 1

Target A1C Goals

For this patient with A1C 10.0%:

• Initial target: A1C <7% for most nonpregnant adults 2
• More stringent target of <6.5% may be appropriate if short diabetes duration, no cardiovascular disease, and achievable without hypoglycemia 2
• Less stringent target of <8% only if patient has limited life expectancy, extensive comorbidities, or high hypoglycemia risk 2

Common Pitfalls to Avoid

Key safety considerations:

• Withhold dapagliflozin 3 days before major surgery or prolonged fasting to reduce ketoacidosis risk 1
• Do not use if history of serious hypersensitivity to dapagliflozin (anaphylaxis/angioedema reported) 1
• Avoid in type 1 diabetes due to significantly increased ketoacidosis risk 1
• Ensure adequate hydration, especially in elderly patients or those on diuretics 1

When Combination Therapy May Be Insufficient

If A1C remains >8% after 3-6 months on maximum Xigduo dose:

• Consider adding basal insulin as the next step, particularly given the severity of hyperglycemia 6
• Alternative: Add GLP-1 receptor agonist (liraglutide preferred for cardiovascular benefits if ASCVD present) 2
• Combination of SGLT2 inhibitor + GLP-1 RA is reasonable and may provide additive benefits on weight and blood pressure 2

Cardiovascular Considerations

If patient has established atherosclerotic cardiovascular disease:

• Use dapagliflozin 10 mg daily (not for glycemic control alone, but for cardiovascular risk reduction) 2
• Empagliflozin is currently preferred SGLT2 inhibitor for cardiovascular outcomes based on strongest evidence, though dapagliflozin also shows benefit 2
• Initiate at lowest dose (10 mg for dapagliflozin); no dose titration needed for cardiovascular benefits 2