Inhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes

Galina Smushkin, Adrian VellaDivision of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN, USAAbstract: Postprandial hyperglycemia in type 2 diabetes is characterized by impaired insulin secretion and action, decreased glucose effectiveness and defec...

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Autores principales:	Galina Smushkin, Adrian Vella
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2009
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/7e28802b23eb4617abb118b1cd3c1245
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spelling	oai:doaj.org-article:7e28802b23eb4617abb118b1cd3c12452021-12-02T00:13:45ZInhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes1178-7007https://doaj.org/article/7e28802b23eb4617abb118b1cd3c12452009-06-01T00:00:00Zhttp://www.dovepress.com/inhibition-of-dipeptidyl-peptidase-4-the-mechanisms-of-action-and-clin-a3253https://doaj.org/toc/1178-7007Galina Smushkin, Adrian VellaDivision of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN, USAAbstract: Postprandial hyperglycemia in type 2 diabetes is characterized by impaired insulin secretion and action, decreased glucose effectiveness and defective suppression of glucagon secretion. Newly available therapies for type 2 diabetes target the pathway of the incretin hormone glucagon-like peptide-1 (GLP-1). Oral inhibitors of dipeptidyl peptidase-4 (DPP-4) raise the level of endogenous GLP-1 by inhibiting its clearance thereby lowering fasting and postprandial glucose concentrations. Unlike compounds which act as agonists of the GLP-1 receptor, DPP-4 inhibitors are not associated with significant effects on gastrointestinal motility, which led to a controversy around the mechanisms responsible for their glucose-lowering effects. Here we review the evidence in regards to the mechanisms whereby DPP-4 inhibitors lower glucose concentrations. Their effects are most likely mediated by an increase in endogenous GLP-1, although additional mechanisms may be involved. The pharmacology, efficacy and safety of vildagliptin, a novel DPP-4 inhibitor, are also discussed.Keywords: insulin secretion, insulin action, incretin, DPP-4 inhibitor, glucagon-like peptide 1 Galina SmushkinAdrian VellaDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2009, Iss default, Pp 83-90 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Galina Smushkin Adrian Vella Inhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes
description	Galina Smushkin, Adrian VellaDivision of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN, USAAbstract: Postprandial hyperglycemia in type 2 diabetes is characterized by impaired insulin secretion and action, decreased glucose effectiveness and defective suppression of glucagon secretion. Newly available therapies for type 2 diabetes target the pathway of the incretin hormone glucagon-like peptide-1 (GLP-1). Oral inhibitors of dipeptidyl peptidase-4 (DPP-4) raise the level of endogenous GLP-1 by inhibiting its clearance thereby lowering fasting and postprandial glucose concentrations. Unlike compounds which act as agonists of the GLP-1 receptor, DPP-4 inhibitors are not associated with significant effects on gastrointestinal motility, which led to a controversy around the mechanisms responsible for their glucose-lowering effects. Here we review the evidence in regards to the mechanisms whereby DPP-4 inhibitors lower glucose concentrations. Their effects are most likely mediated by an increase in endogenous GLP-1, although additional mechanisms may be involved. The pharmacology, efficacy and safety of vildagliptin, a novel DPP-4 inhibitor, are also discussed.Keywords: insulin secretion, insulin action, incretin, DPP-4 inhibitor, glucagon-like peptide 1
format	article
author	Galina Smushkin Adrian Vella
author_facet	Galina Smushkin Adrian Vella
author_sort	Galina Smushkin
title	Inhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes
title_short	Inhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes
title_full	Inhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes
title_fullStr	Inhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes
title_full_unstemmed	Inhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes
title_sort	inhibition of dipeptidyl peptidase-4: the mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes
publisher	Dove Medical Press
publishDate	2009
url	https://doaj.org/article/7e28802b23eb4617abb118b1cd3c1245
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Inhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes

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