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Gut hormone polyagonists for the treatment of type 2 diabetes.
Peptides 100, 190-201 (2018)
Chemical derivatives of the gut-derived peptide hormone glucagon-like peptide 1 (GLP-1) are among the best-in-class pharmacotherapies to treat obesity and type 2 diabetes. However, GLP-1 analogs have modest weight lowering capacity, in the range of 5-10%, and the therapeutic window is hampered by dose-dependent side effects. Over the last few years, a new concept has emerged: combining the beneficial effects of several key metabolic hormones into a single molecular entity. Several unimolecular GLP-1-based polyagonists have shown superior metabolic action compared to GLP-1 monotherapies. In this review article, we highlight the history of polyagonists targeting the receptors for GLP-1, GIP and glucagon, and discuss recent progress in expanding of this concept to now allow targeted delivery of nuclear hormones via GLP-1 and other gut hormones, as a novel approach towards more personalized pharmacotherapies.
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Publication type
Article: Journal article
Document type
Review
Keywords
Glp-1/glucagon Co-agonism ; Polypharmacology ; Type 2 Diabetes ; Gip; Dependent Insulinotropic Polypeptide; Gastric-inhibitory Polypeptide; Glucagon-like Peptide-1; Term Weight Control; Glp-1 Receptor Agonists; High-fat Diet; Topiramate Extended-release; Prohormone Convertase Pc2; Pancreatic Beta-cells; In-vivo
ISSN (print) / ISBN
0196-9781
e-ISSN
1873-5169
Journal
Peptides
Quellenangaben
Volume: 100,
Pages: 190-201
Publisher
Elsevier
Publishing Place
New York, NY
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)