Can Farxiga (dapagliflozin) be added to a patient's regimen while they are already taking metformin, or must metformin be discontinued first?

Adding Farxiga to Metformin

You can and should add Farxiga (dapagliflozin) to metformin without discontinuing metformin—in fact, metformin should be continued as the foundation of therapy while adding dapagliflozin as combination treatment. 1

Guideline-Based Recommendation

The American Diabetes Association explicitly states that once metformin is initiated, it should be continued as long as it is tolerated and not contraindicated, with other agents (including SGLT2 inhibitors like dapagliflozin) added to metformin rather than replacing it. 1 This represents the standard approach to intensifying diabetes therapy.

For patients with type 2 diabetes and chronic kidney disease who require additional glucose-lowering beyond metformin, SGLT2 inhibitors should be considered as add-on therapy specifically because they reduce risks of CKD progression, cardiovascular events, and hypoglycemia. 1

Clinical Evidence Supporting Combination Therapy

The FDA-approved indication for dapagliflozin includes use as add-on therapy to metformin, supported by robust clinical trial data:

• In a 24-week placebo-controlled trial, adding dapagliflozin 10 mg to metformin (≥1,500 mg/day) reduced HbA1c by an additional 0.5% compared to metformin alone, with 40.6% of patients achieving HbA1c <7% versus 25.9% on metformin alone. 2

• At 102 weeks, dapagliflozin added to metformin sustained HbA1c reductions of 0.78% (for the 10 mg dose), along with sustained weight loss of 1.74 kg and fasting plasma glucose reductions. 3

• The combination provides complementary mechanisms: metformin reduces hepatic glucose production and improves insulin sensitivity, while dapagliflozin increases urinary glucose excretion independent of insulin. 4

Practical Implementation Algorithm

Step 1: Verify eligibility for dapagliflozin

• Check eGFR ≥45 mL/min/1.73 m² (dapagliflozin requires adequate renal function). 5
• Confirm metformin is not contraindicated (eGFR ≥30 mL/min/1.73 m²). 1

Step 2: Continue metformin at current dose

• Maintain metformin at effective dose (typically 2,000 mg daily or 1,000 mg twice daily). 6
• Do not reduce or discontinue metformin when adding dapagliflozin. 1

Step 3: Initiate dapagliflozin

• Start dapagliflozin 10 mg once daily (standard dose for add-on therapy). 2
• No dose titration of dapagliflozin is required. 2

Step 4: Monitor for response and adverse effects

• Expect additional HbA1c reduction of 0.5-0.8%, weight loss of 2-3 kg, and systolic blood pressure reduction of 4-5 mmHg within 24 weeks. 5, 2
• Monitor for genital infections (occurs in 11.7-14.6% of patients) and urinary tract infections (8.0-13.3%). 3

Critical Safety Considerations

Metformin continuation is safe with dapagliflozin, but be aware of rare metabolic acidosis risks:

• While both drugs can theoretically contribute to metabolic acidosis (lactic acidosis with metformin, euglycemic diabetic ketoacidosis with SGLT2 inhibitors), the combination is FDA-approved and widely used. 7

• Educate patients about signs of diabetic ketoacidosis (nausea, vomiting, abdominal pain, fatigue) even with normal glucose levels, particularly during illness, fasting, or surgery. 1, 5

• Temporarily discontinue both medications during acute illness with risk of lactic acidosis (sepsis, hypoxia, acute kidney injury) or before iodinated contrast procedures if eGFR <60 mL/min/1.73 m². 1

Additional Benefits of Combination Therapy

Beyond glycemic control, the dapagliflozin-metformin combination offers cardiovascular and renal benefits:

• For patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, SGLT2 inhibitors like dapagliflozin are specifically recommended as part of the antihyperglycemic regimen alongside metformin. 1

• Dapagliflozin reduces the rate of cardiovascular death or hospitalization for heart failure and may reduce progression of renal disease. 8

• The combination has a low risk of hypoglycemia since neither agent directly stimulates insulin secretion. 3, 9

Common Pitfalls to Avoid

• Do not discontinue metformin when adding dapagliflozin—this contradicts guideline recommendations and removes the benefits of first-line therapy. 1

• Do not fail to check renal function before initiating dapagliflozin—it requires eGFR ≥45 mL/min/1.73 m² for initiation. 5

• Do not ignore the need for patient education about ketoacidosis risk—even though rare, euglycemic DKA is a serious complication that patients must recognize. 1, 5

• Do not forget to monitor vitamin B12 levels with long-term metformin use—periodic measurement should be considered, especially in patients with anemia or peripheral neuropathy. 1, 6