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      DPP-4 inhibitors.

      Best Practice & Research. Clinical Endocrinology & Metabolism

      Adamantane, adverse effects, analogs & derivatives, therapeutic use, Animals, Body Weight, drug effects, Diabetes Mellitus, Type 2, drug therapy, Dipeptidyl-Peptidase IV Inhibitors, Drug Therapy, Combination, Glucagon, secretion, Glucagon-Like Peptide 1, antagonists & inhibitors, physiology, Humans, Hypoglycemia, chemically induced, Hypoglycemic Agents, Insulin, Lipid Metabolism, Metformin, Nitriles, Protease Inhibitors, Pyrazines, Pyrrolidines, Substrate Specificity, Thiazolidinediones, Triazoles

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          Inhibition of dipeptidyl peptidase 4 (DPP-4) is a novel treatment for type-2 diabetes. DPP-4 inhibition prevents the inactivation of glucagon-like peptide 1 (GLP-1), which increases levels of active GLP-1. This increases insulin secretion and reduces glucagon secretion, thereby lowering glucose levels. Several DPP-4 inhibitors are in clinical development. Most experience so far has been with sitagliptin (Merck; approved by the FDA) and vildagliptin (Novartis; filed). These are orally active compounds with a long duration, allowing once-daily administration. Both sitagliptin and vildagliptin improve metabolic control in type-2 diabetes, both in monotherapy and in combination with metformin and thiazolidinediones. A reduction in HbA(1c) of approximately 1% is seen in studies of DPP-4 inhibition of up to 52 weeks' duration. DPP-4 inhibition is safe and well tolerated, the risk of hypoglycaemia is minimal, and DPP-4 inhibition is body-weight neutral. DPP-4 inhibition is suggested to be a first-line treatment of type-2 diabetes, particularly in its early stages in combination with metformin. However, the durability and long-term safety of DPP-4 inhibition remain to be established.

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