Evaluating the Evidence behind the Novel Strategy of Early Combination from Vision to Implementation

Type 2 diabetes mellitus (T2DM) is a complex and progressive chronic disease characterised by elevating hyperglycaemia and as-sociated need to gradually intensify therapy in order to achieve and maintain glycaemic control. Treating hyperglycaemia with se-quential therapy is proposed to allow holistic assessment of the efficacy and risk-to-benefit ratio of each added component. How-ever, there is an array of evidence supporting the scientific rationale for using synergistic, earlier, modern drug combinations to achieve glycaemic goals, delay the deterioration of glycaemic control, and, therefore, potentially preserve or slow down the declin-ing β-cell function. Additionally, implementation of early combination(s) may lead to opportunities to combat clinical inertia and other hurdles to optimised disease management outcomes. This review aims to discuss the latest empirical evidence for long-term clinical benefits of this novel strategy of early combination in people with newly diagnosed T2DM versus the current widely-im-plemented treatment paradigm, which focuses on control of hyperglycaemia using lifestyle interventions followed by sequentially intensified (mostly metformin-based) monotherapy. The recent reported Vildagliptin Efficacy in combination with metfoRmin For earlY treatment of T2DM (VERIFY) study results have provided significant new evidence confirming long-term glycaemic durability and tolerability of a specific early combination in the management of newly diagnosed, treatment-naïve patients world-wide. These results have also contributed to changes in clinical treatment guidelines and standards of care while clinical imple-mentation and individualised treatment decisions based on VERIFY results might face barriers beyond the existing scientific evi-dence.Peer reviewe