Diabetes and obesity treatment based on dual incretin receptor activation: ‘twincretins’

May 11, 2016Diabetes, obesity & metabolism

Treating diabetes and obesity by activating two hormone receptors called 'twincretins'

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Abstract

New drugs designed to co-activate both the GIP receptor and the GLP-1 receptor may provide more effective treatment options for diabetes and obesity.

GLP-1 helps regulate insulin secretion and appetite, while GIP is associated with lipid metabolism.
Combining the effects of GIP and GLP-1 could enhance β cell function and reduce adverse effects compared to GLP-1 receptor agonists alone.
Research includes in vitro studies, animal studies, and human trials on the co-administration of GIP and GLP-1.
Recent advancements focus on a newly developed GIPR/GLP-1R co-agonist, showing potential benefits in treating diabetes and obesity.
Challenges and promising areas in the development of incretin dual agonists are currently being explored.

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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.

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Diabetes and obesity treatment based on dual incretin receptor activation: ‘twincretins’

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