Glucagon-like Peptide-1 Analogues for Type 2 Diabetes Mellitus
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REVIEW ARTICLE
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Glucagon-like Peptide–1 Analogues for Type 2 Diabetes Mellitus Current and Emerging Agents Baptist Gallwitz Medizinische Klinik IV, Eberhard-Karls University, Tu¨bingen, Germany
Contents Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. The Need for Further Treatment Options in Type 2 Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . 2. The Physiology of Incretin Hormones in Health and Type 2 Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Glucagon-like Peptide (GLP)-1 Receptor Agonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Exenatide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Liraglutide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. GLP-1 Receptor Agonists and Their Place in Guidelines for Type 2 Diabetes Therapy . . . . . . . . . . . . 5. Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Long-Acting GLP-1 Receptor Agonist: Exenatide Once Weekly . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Other Long-Acting GLP-1 Receptor Agonists in Development . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 GLP-1 Receptor Agonists and Their Potential in Type 1 Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . 6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Abstract
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Novel therapeutic options for type 2 diabetes mellitus based on the action of the incretin hormone glucagon-like peptide (GLP)-1 were introduced in 2005. As injectable GLP-1 receptor agonists acting on the GLP-1 receptor, exenatide and liraglutide are available in many countries. In type 2 diabetes treatment, incretinbased therapies are attractive and more commonly used because of their mechanism of action and safety profile. Stimulation of insulin secretion and inhibition of glucagon secretion by these agents occur in a glucose-dependent manner. Therefore, incretin-based therapies have no intrinsic risk for hypoglycaemia. Furthermore, GLP-1 receptor agonists allow weight loss and lower systolic blood pressure. This review gives a brief overview of the mechanism of action and summarizes the clinical data available on exenatide and liraglutide as established substances. It further highlights the clinical study data of exenatide once weekly as the first long-acting GLP-1 receptor agonist and covers other new long acting GLP-1 receptor agonists currently in clinical development. The pla
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