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NEW ORAL ANTIDIABETIC DRUGS: DPP-4 INHIBITORS AND INCRETIN MIMETICS Nebojša M. Lalić

Introduction Treatment of hyperglycemia in type 2 diabetes involves a wide spectrum of different therapeutic approaches, particularly of oral agents, which are available to be used in an attempt to achieve normoglycemia otherwise postulated to be the major goal of this treatment. (1) However, the longterm studies have shown that the sustainable or “definitive” achievement of the persistent normoglycemia on the treatment with any of those particular agents or their combinations is not yet feasible. (2) In the recent years the studies have strongly emphasized the need for the recruitment of the new therapeutic agents and modalities which could bring in some advances in the possibilities of obtaining the persistent optimal glycoregulation. In this context, the agents acting on the level incretin effect, named as incretin mimetics and DPP-4 inhibitors, have been introduced in the treatment of type 2 diabetes, offering new therapeutic advantages which are still under intensive investigations of many ongoing studies. In this chapter we will discuss (a) the present state of the use of oral agents in type 2 diabetes treatment, (b) the incretin effect and the role of glucagon-like peptide 1 (GLP-1), (c) the therapeutic effects of incretin-based treatment: DPP-4 inhibitors and incretin mimetics and (d) the positioning of the incretin-based therapeutic agents in the recommendations for type 2 diabetes treatment. The use of oral agents in type 2 diabetes treatment: present state The last decade has been characterized by a continuous upgrading of clinical recommendations for the treatment of hyperglycemia in type 2 diabetes in order to meet more efficiently the postulated requirement of obtaining near-normoglycemia. The process culminated in adoption of the consensus statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) from 2009 which reaffirmed and synthesized the prevailing international recommendations in this area (3) The consensus statement has brought in some very important changes in the use of oral agents. Following the previous versions of the consensus statement of 2006 and 2008 (4), this statement has reestablished the threshold value of the glycated hemoglobin (HbA1c) of 7% as a marker of the treatment failure when switching from one level of treatment to the more complex one. Also,


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