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Dual and triple incretin-based co-agonists: Novel therapeutics for obesity and diabetes.

Diabetes Ther. 15, 1069-1084 (2024)
DOI PMC
Creative Commons Lizenzvertrag
The discovery of long-acting incretin receptor agonists represents a major stride forward in tackling the dual epidemic of obesity and diabetes. Here we outline the evolution of incretin-based pharmacotherapy, from exendin-4 to the discovery of the multi-incretin hormone receptor agonists that look set to be our next step toward curing diabetes and obesity. We discuss the multiagonists currently in clinical trials and the improvement in efficacy each new generation of these drugs bring. The success of these agents in preclinical models and clinical trials suggests a promising future for multiagonists in the treatment of metabolic diseases, with the most recent glucose-dependent insulinotropic peptide receptor:glucagon-like peptide 1 receptor:glucagon receptor (GIPR:GLP-1R:GCGR) triagonists rivaling the efficacy of bariatric surgery. However, further research is needed to fully understand how these therapies exert their effect on body weight and in the last section we cover open questions about the potential mechanisms of multiagonist drugs, and the understanding of how gut-brain communication can be leveraged to achieve sustained body weight loss without adverse effects.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Diabetes ; Dual-agonist ; Gip ; Glp-1 ; Glucagon ; Incretin ; Obesity ; Triagonist; Dependent Insulinotropic Polypeptide; Glucagon-like Peptide-1; Gastric-inhibitory Polypeptide; Receptor Agonist; Double-blind; Glycemic Control; Cardiovascular Outcomes; Exenatide Exendin-4; Recombinant Leptin; Lipoprotein-lipase
ISSN (print) / ISBN 1869-6961
e-ISSN 1869-6953
Quellenangaben Volume: 15, Issue: 5, Pages: 1069-1084 Article Number: , Supplement: ,
Publisher Springer
Publishing Place New York, NY [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Grants European Research Council