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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)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter 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
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Zeitschrift Cell Metabolism
Quellenangaben Band: 35, Heft: 9, Seiten: 1519-1529 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
POF Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502200-001
G-501900-221
Förderungen 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
DOI 10.1016/j.cmet.2023.07.010
WOS ID 001138180700001
Scopus ID 85169023000
PubMed ID 37591245
Erfassungsdatum 2023-10-06
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