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

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Glucagon-like peptide-1 receptor agonists for type 2 diabetes : A rational drug development. / Ahrén, Bo.

In: Journal of Diabetes Investigation, Vol. 10, No. 2, 2019, p. 196-201.

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TY - JOUR

T1 - Glucagon-like peptide-1 receptor agonists for type 2 diabetes

T2 - Journal of Diabetes Investigation

AU - Ahrén, Bo

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Glucagon-like peptide-1

KW - Treatment

KW - Type 2 diabetes

U2 - 10.1111/jdi.12911

DO - 10.1111/jdi.12911

M3 - Article

VL - 10

SP - 196

EP - 201

JO - Journal of Diabetes Investigation

JF - Journal of Diabetes Investigation

SN - 2040-1116

IS - 2

ER -