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Brandt, S. ; Götz, A. ; Tschöp, M.H. ; Müller, T.D.

Gut hormone polyagonists for the treatment of type 2 diabetes.

Peptides 100, 190-201 (2018)
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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
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 0196-9781
e-ISSN 1873-5169
Journal Peptides
Quellenangaben Volume: 100, Issue: , Pages: 190-201 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
POF-Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-501900-221
G-502200-001
DOI 10.1016/j.peptides.2017.12.021
WOS ID WOS:000424642600026
Scopus ID 85041458811
PubMed ID 29412819
Erfassungsdatum 2018-03-12
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