Metformin and Dapagliflozin Combination Therapy for Type 2 Diabetes Mellitus

Rationale for Combination Therapy

The European Society of Cardiology guidelines recommend the combination of metformin and SGLT2 inhibitors like dapagliflozin for optimal management of T2DM 3, 4
First-line treatment of T2DM in patients with or at risk for heart failure should include both metformin and SGLT2 inhibitors like dapagliflozin 3

For patients with eGFR ≥30 ml/min/1.73 m², metformin should be administered at a dose of 1000 mg daily 1, 2
For patients with eGFR 30-44 ml/min/1.73 m², maintain metformin at a maximum dose of 1000 mg daily 2
For patients with eGFR 45-59 ml/min/1.73 m², consider dose reduction if they have conditions predisposing to hypoperfusion or hypoxemia 2
Metformin should not be initiated or continued if eGFR is <30 ml/min/1.73 m² 1, 2

Monitor eGFR at least annually in all patients, increasing to every 3-6 months when eGFR falls below 60 ml/min/1.73 m² 2
Monitor for vitamin B12 deficiency in patients treated with metformin for more than 4 years 1
Assess for signs of lactic acidosis, especially during periods of acute illness that may cause dehydration or hypoxemia 2
Implement a sick day protocol to temporarily hold metformin during acute illness, surgery, or procedures requiring contrast dye 2

Monitor for genital mycotic infections, which occur in approximately 6% of patients on SGLT2 inhibitors 5
Assess volume status, especially in patients on multiple medications that can affect fluid balance 5
Be vigilant for euglycemic diabetic ketoacidosis, particularly during periods of acute illness or reduced food intake 5