Fixed-Dose Combination of Dapagliflozin + Sitagliptin + Metformin in Patients with Type 2 Diabetes Poorly Controlled with Metformin: Phase 3, Randomized Comparison with Dual Combinations.

Type 2 diabetes is a progressive disease in which the risks of microvascular and macrovascular complications and mortality are strongly associated with hyperglycemia. Achieving glycemic control remains the main goal of treatment to prevent these complications. Estimates in 2019 showed that 77 million individuals had diabetes in India, which is expected to rise over 134 million by 2045. Considering the progressive nature of the disease, many guidelines recommend use of dual or triple drug therapy based on glycated hemoglobin (HbA1c) level. Use of fixed-dose combination (FDC) helps to improve therapy compliance and can provide optimum therapeutic benefits. Mechanisms of action of dipeptidyl peptidase 4 (DPP4) and sodium­glucose cotransporter 2 (SGLT2) inhibitors are complementary to that of metformin with low risk of hypoglycemia. Studies have shown beneficial effects of adding both DPP4 inhibitors and SGLT2 inhibitors after metformin monotherapy. This phase 3 study was designed to assess efficacy and safety of triple FDC of dapagliflozin + sitagliptin + metformin extended release in comparison with combipack of sitagliptin + metformin sustained release and FDC of dapagliflozin + metformin ER in patients with type 2 diabetes inadequately controlled with metformin monotherapy. The study demonstrated superiority of triple FDC of dapagliflozin + sitagliptin + metformin ER over dual combinations in terms of reduction in HbA1c and percentage of patients achieving target HbA1c at the end of week 16. The current study provides evidence for considering triple FDC of dapagliflozin + sitagliptin + metformin ER as an alternative option with minimal risk of hypoglycemia and weight gain, while considering oral triple-combination therapy for patients to achieve their glycemic target.