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

Publication ,  Journal Article
Campbell, JE; Müller, TD; Finan, B; DiMarchi, RD; Tschöp, MH; D'Alessio, DA
Published in: Cell metabolism
September 2023

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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Published In

Cell metabolism

DOI

EISSN

1932-7420

ISSN

1550-4131

Publication Date

September 2023

Volume

35

Issue

9

Start / End Page

1519 / 1529

Related Subject Headings

  • Weight Loss
  • Receptors, G-Protein-Coupled
  • Incretins
  • Hyperglycemia
  • Humans
  • Endocrinology & Metabolism
  • Diabetes Mellitus
  • Body Weight
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology
 

Citation

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Campbell, J. E., Müller, T. D., Finan, B., DiMarchi, R. D., Tschöp, M. H., & D’Alessio, D. A. (2023). GIPR/GLP-1R dual agonist therapies for diabetes and weight loss-chemistry, physiology, and clinical applications. Cell Metabolism, 35(9), 1519–1529. https://doi.org/10.1016/j.cmet.2023.07.010
Campbell, Jonathan E., Timo D. Müller, Brian Finan, Richard D. DiMarchi, Matthias H. Tschöp, and David A. D’Alessio. “GIPR/GLP-1R dual agonist therapies for diabetes and weight loss-chemistry, physiology, and clinical applications.Cell Metabolism 35, no. 9 (September 2023): 1519–29. https://doi.org/10.1016/j.cmet.2023.07.010.
Campbell JE, Müller TD, Finan B, DiMarchi RD, Tschöp MH, D’Alessio DA. GIPR/GLP-1R dual agonist therapies for diabetes and weight loss-chemistry, physiology, and clinical applications. Cell metabolism. 2023 Sep;35(9):1519–29.
Campbell, Jonathan E., et al. “GIPR/GLP-1R dual agonist therapies for diabetes and weight loss-chemistry, physiology, and clinical applications.Cell Metabolism, vol. 35, no. 9, Sept. 2023, pp. 1519–29. Epmc, doi:10.1016/j.cmet.2023.07.010.
Campbell JE, Müller TD, Finan B, DiMarchi RD, Tschöp MH, D’Alessio DA. GIPR/GLP-1R dual agonist therapies for diabetes and weight loss-chemistry, physiology, and clinical applications. Cell metabolism. 2023 Sep;35(9):1519–1529.
Journal cover image

Published In

Cell metabolism

DOI

EISSN

1932-7420

ISSN

1550-4131

Publication Date

September 2023

Volume

35

Issue

9

Start / End Page

1519 / 1529

Related Subject Headings

  • Weight Loss
  • Receptors, G-Protein-Coupled
  • Incretins
  • Hyperglycemia
  • Humans
  • Endocrinology & Metabolism
  • Diabetes Mellitus
  • Body Weight
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology