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Harger, A. ; Stemmer, K. ; Tschöp, M.H. ; Müller, T.D.

Incretin-based co- and tri-agonists Innovative polypharmacology for the treatment of obesity and diabetes.

Incretin-based co- and tri-agonists: Innovative polypharmacology for the treatment of obesity and diabetes.

Internist 60, 895-902 (2019)
Postprint DOI PMC
Open Access Green
Background The worldwide rise in overweight and obesity is paralleled by an increasing prevalence of type-2 diabetes. Apart from bariatric surgery, treatment options to decrease body weight are often underwhelming. Innovative pharmacological options are required to cope with the global "diabesity" pandemic. Objectives Particular novel pharmacological approaches are discussed, with a special focus on polyagonist-based pharmacotherapies. Materials and methods Articles on co- and tri-agonists for the treatment of obesity and diabetes are presented and discussed. Results Unimolecular peptides have been developed for the treatment of obesity and type-2 diabetes. These peptides activate the receptors of multiple hormones and bundle their positive effects in one single molecule. In preclinical studies, polyagonists targeting the receptors for glucagon-like peptide-1 (GLP-1), glucagon, or glucose-dependent insulinotropic peptide (GIP) were promising to reduce body weight and blood glucose. GLP-1-mediated delivery of the nuclear hormones estrogen or dexamethasone also yielded beneficial effects in preclinical studies of obesity. Conclusions Polyagonists represent an innovative strategy for the development of novel pharmacotherapies to treat obesity and diabetes.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Overweight ; Blood Glucose ; Glucagon-like Peptide 1 ; Glucose-dependent Insulinotropic Peptide ; Weight Loss; Glucagon Receptor Antagonist; Gastric-inhibitory Polypeptide; Type-2; Pharmacology; Pharmacodynamics; Pharmacokinetics; Ly2409021; Glucose; Biology; Safety
ISSN (print) / ISBN 0020-9554
e-ISSN 1432-1289
Journal Internist, Der
Quellenangaben Volume: 60, Issue: 9, Pages: 895-902 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Berlin ; Heidelberg
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)