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

Ahrén, Bo LU (2018) In Journal of Diabetes Investigation
Abstract

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.... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Glucagon-like peptide-1, Treatment, Type 2 diabetes
in
Journal of Diabetes Investigation
publisher
Wiley-Blackwell
external identifiers
  • scopus:85053465715
ISSN
2040-1116
DOI
10.1111/jdi.12911
language
English
LU publication?
yes
id
1be87b5e-45d6-4ee0-9d32-b8d1586fb666
date added to LUP
2018-10-22 10:41:10
date last changed
2019-02-20 11:32:34
@article{1be87b5e-45d6-4ee0-9d32-b8d1586fb666,
  abstract     = {<p>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.</p>},
  author       = {Ahrén, Bo},
  issn         = {2040-1116},
  keyword      = {Glucagon-like peptide-1,Treatment,Type 2 diabetes},
  language     = {eng},
  month        = {08},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Diabetes Investigation},
  title        = {Glucagon-like peptide-1 receptor agonists for type 2 diabetes : A rational drug development},
  url          = {http://dx.doi.org/10.1111/jdi.12911},
  year         = {2018},
}