From the FDA Drug Label
At Week 24, treatment with dapagliflozin 10 mg QAM provided significant improvements in HbA1c and the fasting plasma glucose (FPG) compared with placebo A total of 1236 treatment-naive adult patients with inadequately controlled type 2 diabetes mellitus (HbA1c ≥7. 5% and ≤12%) participated in 2 active-controlled trials of 24-week duration to evaluate initial therapy with dapagliflozin 5 mg or 10 mg in combination with metformin extended-release (XR) formulation The combination treatment of dapagliflozin 10 mg plus metformin XR provided statistically significant improvements in HbA1c and FPG compared with either of the monotherapy treatments and statistically significant reduction in body weight compared with metformin XR alone
The FDA drug label does not answer the question about basal insulin initiation for patients on dapagliflozin and metformin.
From the Research
For patients on dapagliflozin and metformin who require basal insulin initiation, start with a once-daily long-acting insulin such as insulin glargine (10 units or 0.1-0.2 units/kg/day) or insulin detemir, preferably at bedtime, as this regimen has been shown to provide effective glycemic control with minimal risk of hypoglycemia 1.
Key Considerations
- Continue both dapagliflozin and metformin alongside insulin as this triple therapy provides complementary mechanisms of action, improving insulin sensitivity, reducing glucose reabsorption in the kidneys, and addressing insufficient endogenous insulin production 2, 3, 4.
- Monitor fasting blood glucose levels daily and adjust insulin dose by 2-4 units every 3-7 days until target fasting glucose of 80-130 mg/dL is achieved, to minimize the risk of hypoglycemia and optimize glycemic control 1.
- Be vigilant for hypoglycemia, especially at night, and educate patients on recognition and management of low blood sugar, as the combination of basal insulin and dapagliflozin may increase the risk of hypoglycemia 5.
- Consider reducing the dapagliflozin dose if the patient experiences volume depletion or has renal impairment, as SGLT2 inhibitors like dapagliflozin may increase the risk of these adverse effects 3, 4.
- Ensure adequate hydration and monitor for diabetic ketoacidosis, which can occur with SGLT2 inhibitors like dapagliflozin even at relatively normal blood glucose levels, as this is a rare but potentially life-threatening complication 2, 1.
Benefits of Combination Therapy
- The combination of metformin, dapagliflozin, and basal insulin provides comprehensive glycemic control through multiple pathways, improving insulin sensitivity, reducing glucose reabsorption in the kidneys, and addressing insufficient endogenous insulin production 2, 3, 4.
- This combination therapy has been shown to reduce the risk of hypoglycemia and cardiovascular events, while also promoting weight loss and improving blood pressure control 3, 4, 1.
- The use of a fixed-dose combination therapy such as dapagliflozin-metformin XR can increase medication adherence and patient satisfaction, and improve glycemic control 4.