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Glucagon‐like peptide‐1 receptor agonists for type 2 diabetes: A rational drug development

Today, glucagon‐like peptide‐1 (GLP‐1) receptor agonists are established glucose‐lowering drugs used in the management of type 2 diabetes. Their development emerged from the understanding that a combined islet dysfunction comprising of impaired insulin secretion and exaggerated glucagon secretion is...

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Autor principal: Ahrén, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400152/
https://www.ncbi.nlm.nih.gov/pubmed/30099845
http://dx.doi.org/10.1111/jdi.12911
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author Ahrén, Bo
author_facet Ahrén, Bo
author_sort Ahrén, Bo
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description Today, glucagon‐like peptide‐1 (GLP‐1) receptor agonists are established glucose‐lowering drugs used in the management of type 2 diabetes. Their development emerged from the understanding that a combined islet dysfunction comprising of impaired insulin secretion and exaggerated glucagon secretion is the key defect of hyperglycemia. GLP‐1 was shown to target these defects, and after the discovery that dipeptidyl peptidase‐4 inactivates native GLP‐1, several different dipeptidyl peptidase‐4‐resistant GLP‐1 receptor agonists have been developed. They are administered subcutaneously, but show differences in molecular structure, molecular size and pharmacokinetics, the latter allowing twice‐daily, once‐daily or once‐weekly administration. They have been shown to be efficient in reducing both glycated hemoglobin and bodyweight, and to be safe and highly tolerable. Cardiovascular outcomes trials have shown them to be neutral or beneficial. GLP‐1 receptor agonists are positioned as add‐ons to metformin alone or in combination with oral agents in the clinical paradigm. They are also efficient when combined with insulin, and fixed dose combinations with long‐acting insulin have been developed. Recent development includes a very long administration schedule and oral availability. The research from the first demonstration of the antidiabetic action of GLP‐1 in the early 1990s to the enormously accumulated data today represents a successful and rational development, which has been characterized by focused perseverance to establish this therapy in the management of type 2 diabetes.
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spelling pubmed-64001522019-03-14 Glucagon‐like peptide‐1 receptor agonists for type 2 diabetes: A rational drug development Ahrén, Bo J Diabetes Investig Mini Review Today, glucagon‐like peptide‐1 (GLP‐1) receptor agonists are established glucose‐lowering drugs used in the management of type 2 diabetes. Their development emerged from the understanding that a combined islet dysfunction comprising of impaired insulin secretion and exaggerated glucagon secretion is the key defect of hyperglycemia. GLP‐1 was shown to target these defects, and after the discovery that dipeptidyl peptidase‐4 inactivates native GLP‐1, several different dipeptidyl peptidase‐4‐resistant GLP‐1 receptor agonists have been developed. They are administered subcutaneously, but show differences in molecular structure, molecular size and pharmacokinetics, the latter allowing twice‐daily, once‐daily or once‐weekly administration. They have been shown to be efficient in reducing both glycated hemoglobin and bodyweight, and to be safe and highly tolerable. Cardiovascular outcomes trials have shown them to be neutral or beneficial. GLP‐1 receptor agonists are positioned as add‐ons to metformin alone or in combination with oral agents in the clinical paradigm. They are also efficient when combined with insulin, and fixed dose combinations with long‐acting insulin have been developed. Recent development includes a very long administration schedule and oral availability. The research from the first demonstration of the antidiabetic action of GLP‐1 in the early 1990s to the enormously accumulated data today represents a successful and rational development, which has been characterized by focused perseverance to establish this therapy in the management of type 2 diabetes. John Wiley and Sons Inc. 2018-09-17 2019-03 /pmc/articles/PMC6400152/ /pubmed/30099845 http://dx.doi.org/10.1111/jdi.12911 Text en © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Mini Review
Ahrén, Bo
Glucagon‐like peptide‐1 receptor agonists for type 2 diabetes: A rational drug development
title Glucagon‐like peptide‐1 receptor agonists for type 2 diabetes: A rational drug development
title_full Glucagon‐like peptide‐1 receptor agonists for type 2 diabetes: A rational drug development
title_fullStr Glucagon‐like peptide‐1 receptor agonists for type 2 diabetes: A rational drug development
title_full_unstemmed Glucagon‐like peptide‐1 receptor agonists for type 2 diabetes: A rational drug development
title_short Glucagon‐like peptide‐1 receptor agonists for type 2 diabetes: A rational drug development
title_sort glucagon‐like peptide‐1 receptor agonists for type 2 diabetes: a rational drug development
topic Mini Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400152/
https://www.ncbi.nlm.nih.gov/pubmed/30099845
http://dx.doi.org/10.1111/jdi.12911
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