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Campbell, J.E.* ; Müller, T.D. ; Finan, B.* ; DiMarchi, R.D.* ; Tschöp, M.H. ; D'Alessio, D.A.*

GIPR/GLP-1R dual agonist therapies for diabetes and weight loss-chemistry, physiology, and clinical applications.

Cell Metab. 35, 1519-1529 (2023)

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Open Access Green as soon as Postprint is submitted to ZB.

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The incretin system is an essential metabolic axis that regulates postprandial metabolism. The two incretin peptides that enable this effect are the glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide 1 (GLP-1), which have cognate receptors (GIPR and GLP-1R) on islet β cells as well as in other tissues. Pharmacologic engagement of the GLP-1R is a proven strategy for treating hyperglycemia in diabetes and reducing body weight. Tirzepatide is the first monomeric peptide with dual activity at both incretin receptors now available for clinical use, and in clinical trials it has shown unprecedented effects to reduce blood glucose and body weight. Here, we discuss the foundational science that led to the development of monomeric multi-incretin receptor agonists, culminating in the development of tirzepatide. We also look to the future of this field and comment on how the concept of multi-receptor agonists will continue to progress for the treatment of metabolic disease.

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Publication type Article: Journal article

Document type Review

Corresponding Author

Keywords Gip ; Glp-1 ; Diabetes ; Incretin ; Obesity ; Tirzepatide; Glucagon-like Peptide-1; Gastric-inhibitory Polypeptide; Glp-1 Receptor Agonist; Dependent Insulinotropic Polypeptide; Body-weight; Glucose-intolerance; Glycemic Control; Adipose-tissue; Induced Nausea; Double-blind

ISSN (print) / ISBN 1550-4131

e-ISSN 1932-7420

Journal Cell Metabolism

Quellenangaben Volume: 35, Issue: 9, Pages: 1519-1529

Publisher Elsevier

Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)

Grants European Research Council ERC AdG HypoFlam
German Center for Diabetes Research (DZD e.V.)
German Research Foundation (DFG)
European Research Council ERC-CoG Trusted
NIH