title: Diabetes and obesity treatment based on dual incretin receptor activation: 'twincretins'.
abstract: 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.
authors.affiliation: Centre for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: M A
authors.initials: MA
authors.lastname: Skow
authors.affiliation: Centre for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: N C
authors.initials: NC
authors.lastname: Bergmann
authors.affiliation: Centre for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|Department of Biomedical Sciences and NNF Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: F K
authors.initials: FK
authors.lastname: Knop
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D054795:Incretins / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists*; D015431:Weight Loss; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; C041086:gastric inhibitory polypeptide receptor; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: co-agonism; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; incretins; obesity therapy; type 2 diabetes