Diabetes Metab J.  2020 Dec;44(6):785-801. 10.4093/dmj.2020.0179.

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

• Paldánius PM

• KMID: 2513043
• DOI: http://doi.org/10.4093/dmj.2020.0179

Abstract

Type 2 diabetes mellitus (T2DM) is a complex and progressive chronic disease characterised by elevating hyperglycaemia and associated need to gradually intensify therapy in order to achieve and maintain glycaemic control. Treating hyperglycaemia with sequential therapy is proposed to allow holistic assessment of the efficacy and risk-to-benefit ratio of each added component. However, 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 declining 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-implemented 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 worldwide. These results have also contributed to changes in clinical treatment guidelines and standards of care while clinical implementation and individualised treatment decisions based on VERIFY results might face barriers beyond the existing scientific evidence.

Keyword

Chronic disease; Diabetes mellitus, type 2; Drug combinations; Early combination strategy; Metformin; Standards of care; Treatment outcome

Figure

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  Fig. 1. Displaying the factors contributing to our established knowledge base, the unmet clinical needs, how these were modified by the key learnings from the Vildagliptin Efficacy in combination with metfoRmin For earlY treatment of T2DM (VERIFY) study while highlighting the aspects of early diabetes care yet to be explored in the future.

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  Fig. 2. Theoretical presentation of the available key evidence along the axis of the extent of glycaemia at diagnosis contrasted against the (known/assumed) duration of the disease at the time of confirmed diagnosis (with corresponding reference). HbA1c, glycosylated hemoglobin; VERIFY, Vildagliptin Efficacy in combination with metfoRmin For earlY treatment of T2DM; ADA, American Diabetes Association; EASD, European Association for the Study of Diabetes.

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