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Diabetes and obesity treatment based on dual incretin receptor activation: ‘twincretins’
Author(s) -
Skow M. A.,
Bergmann N. C.,
Knop F. K.
Publication year - 2016
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12685
Subject(s) - incretin , postprandial , endocrinology , medicine , gastric inhibitory polypeptide , gastric emptying , glucagon like peptide 1 , type 2 diabetes , diabetes mellitus , appetite , agonist , receptor , insulin , glucagon , stomach
The gut incretin hormones glucose‐dependent insulinotropic polypeptide ( GIP ) and glucagon‐like peptide‐1 ( GLP ‐1) are secreted after meal ingestion and work in concert to promote postprandial insulin secretion and regulate glucagon secretion. GLP ‐1 also slows gastric emptying and suppresses appetite, whereas GIP seems to affect lipid metabolism. The introduction of selective GLP ‐1 receptor ( GLP‐1R ) agonists for the treatment of type 2 diabetes and obesity has increased the scientific and clinical interest in incretins. Combining the body weight‐lowering and glucose‐lowering effects of GLP ‐1 with a more potent improvement of β cell function through additional GIP action could potentially offer a more effective treatment of diabetes and obesity, with fewer adverse effects than selective GLP‐1R agonists; therefore, new drugs designed to co‐activate both the GIP receptor ( GIPR ) and the GLP‐1R simultaneously are under development. In the present review, we address advances in the field of GIPR and GLP‐1R co‐agonism and review in vitro studies, animal studies and human trials involving co‐administration of the two incretins, as well as results from a recently developed GIPR / GLP‐1R co‐agonist, and highlight promising areas and challenges within the field of incretin dual agonists.