Role of incretin, incretin analogues and dipeptidyl peptidase 4 inhibitors in the pathogenesis and treatment of diabetes mellitus

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Role of incretin, incretin analogues and dipeptidyl peptidase 4 inhibitors<br /> in the pathogenesis and treatment of diabetes mellitus

Journal Title: Αρχεία Ελληνικής Ιατρικής - Year 2008, Vol 25, Issue 5

Abstract

Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gut-derived incretin hormones that stimulate insulin and suppress glucagon secretion, inhibit gastric emptying, and reduce appetite and food intake. An additional action of GLP-1 is the in vitro inhibition of β-cell apoptosis. GLP-1 can significantly lower plasma glucose in the majority of patients with type 2 diabetes. GLP-1 is inactivated rapidly in vivo by dipeptidyl peptidase 4 (DPP-4) and thus does not appear to be useful as a therapeutic agent in the long-term treatment of diabetes. Therapeutic approaches for enhancing incretin action include degradation-resistant GLP-1 receptor agonists, and inhibitors of DPP-4 activity. Clinical trials with the incretin mimetic exenatide and liraglutide show reduction in fasting and postprandial glucose concentration, and HbA1c, associated with weight loss, but also some nausea and, rarely, vomiting. The DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin) control elevated blood glucose by promoting pancreatic insulin secretion, suppressing pancreatic glucagon secretion, and reducing glucose production by the liver. The DPP-4 inhibitors have shown clinically significant HbA1c reduction with a low risk of hypoglycemia and no effect on body weight, and the potential, based on animal and in vitro studies, for the regeneration and differentiation of pancreatic β-cells. However, long-term clinical studies are needed to determine the benefits of targeting the incretin axis for the treatment of type 2 diabetes.

Authors and Affiliations

S. PAPAS, A. PAPAZAFIROPOULOU

Keywords

glucagon-like peptide

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