From the Guidelines
The combination of dapagliflozin, sitagliptin, and metformin is a recommended triple therapy for type 2 diabetes patients who require additional glycemic control beyond dual therapy, as it provides complementary mechanisms of action and robust HbA1c reduction, according to the most recent guidelines 1.
Mechanism of Action
This combination works through complementary mechanisms:
- metformin decreases hepatic glucose production and improves insulin sensitivity
- sitagliptin (a DPP-4 inhibitor) increases incretin levels to stimulate insulin release and reduce glucagon secretion
- dapagliflozin (an SGLT2 inhibitor) promotes urinary glucose excretion independent of insulin.
Dosage and Administration
Typically, metformin serves as first-line therapy (500-2000mg daily in divided doses), with sitagliptin (100mg daily) and dapagliflozin (5-10mg daily) added sequentially when glycemic targets aren't met.
Benefits and Side Effects
This combination provides robust HbA1c reduction (potentially 1.5-2.0% combined effect), weight loss benefits from dapagliflozin, and cardiovascular and renal protective effects. However, patients should be monitored for side effects including:
- urinary tract infections
- genital mycotic infections
- hypoglycemia (though risk is low)
- rare but serious adverse effects like diabetic ketoacidosis. Adequate renal function should be confirmed before initiating this combination, with dose adjustments needed for patients with reduced kidney function, as supported by previous studies 1.
From the FDA Drug Label
Dapagliflozin has been studied in adult patients as monotherapy, in combination with metformin, pioglitazone, sulfonylurea (glimepiride), sitagliptin (with or without metformin), metformin plus a sulfonylurea, or insulin (with or without other oral antidiabetic therapy), compared to a sulfonylurea (glipizide), and in combination with a GLP-1 receptor agonist (exenatide extended release) added on to metformin.
The combination of dapagliflozin, sitagliptin, and metformin has been studied, as indicated by the text that mentions dapagliflozin in combination with sitagliptin (with or without metformin). Key points about this combination include:
- Dapagliflozin has been shown to produce statistically significant improvements in mean change from baseline at Week 24 in HbA1c compared to control when used in combination with other therapies, including metformin and sitagliptin.
- The specific combination of dapagliflozin, sitagliptin, and metformin is not explicitly detailed in terms of efficacy outcomes, but it is mentioned as part of the broader range of combinations studied 2.
From the Research
Dapagliflozin Sitagliptin Metformin Combination
- The combination of dapagliflozin, sitagliptin, and metformin has been studied as a potential treatment for type 2 diabetes [ 3 ].
- This triple drug fixed-dose combination (FDC) has been compared to dual combinations of sitagliptin + metformin and dapagliflozin + metformin in patients with type 2 diabetes poorly controlled with metformin [ 3 ].
- The results of this study showed that the triple FDC of dapagliflozin + sitagliptin + metformin was significantly better in achieving glycemic control compared to the dual combinations [ 3 ].
Efficacy and Safety
- The triple FDC of dapagliflozin + sitagliptin + metformin resulted in a significantly greater reduction in HbA1c from baseline to week 16 compared to the dual combinations [ 3 ].
- The proportion of patients achieving HbA1c < 7.0% at week 16 was also significantly higher with the triple FDC [ 3 ].
- All study medications were well tolerated, with no significant safety concerns [ 3 ].
Mechanism of Action
- Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor that increases the renal excretion of excess glucose [ 4, 5 ].
- Sitagliptin is a dipeptidyl peptidase-4 inhibitor that increases the levels of incretin hormones, leading to increased insulin secretion and decreased glucagon secretion [ 6 ].
- Metformin is a biguanide that decreases hepatic glucose production and increases insulin sensitivity [ 7, 5 ].