A GLP-1 analogue optimized for cAMP-biased signaling improves weight loss in obese mice
The data demonstrate that biased agonism is a strong predictor of in vivo efficacy for GLP-1R agonists independent of factors like intrinsic cAMP potency or pharmacokinetics. These data suggest that drug discovery screening strategies which take a holistic approach to target receptor signaling may provide more efficacious candidate molecules. The interpretations of these studies are limited by unknowns including how structural modifications to the biased GLP-1R agonist effect physiochemical properties of the molecules.
Authors
- Steffen Reedtz‐Runge (ORCID: https://orcid.org/0000-0002-9216-3311)
- Jonathan D. Douros (ORCID: https://orcid.org/0000-0003-2299-6163)
- Diego Pérez–Tilve (ORCID: https://orcid.org/0000-0002-0351-4133)
- Jenny Norlin (ORCID: https://orcid.org/0000-0002-4825-6975)
- Nikolaj Kulahin Roed
- Jacek Mokrosiński (ORCID: https://orcid.org/0000-0001-5008-0457)
- Wouter F. J. Hogendorf
- Patrick J. Knerr
- Maria Waldhoer (ORCID: https://orcid.org/0000-0003-3534-1959)
- Barent DuBois
- Myrte Merkestein
- Aaron Novikoff (ORCID: https://orcid.org/0000-0002-4838-001X)
- Stephanie A. Mowery
- János T. Kodra
- Timo D. Müller (ORCID: https://orcid.org/0000-0002-0624-9339)
- Rebecca Rohlfs
- Anouk Oldenburger (ORCID: https://orcid.org/0000-0002-0264-2467)
- Robert Augustin
- L. Martini
- Brian Finan
- Lars Linderoth
- Elliot Gerrard
Institutions
- Novo Nordisk (Denmark) (DK)
- Helmholtz Zentrum München (DE)
- Novo Nordisk (United States) (US)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- Heinrich Heine University Düsseldorf (DE)
- Ludwig-Maximilians-Universität München (DE)
- University of Cincinnati Medical Center (US)
Publication Details
- Journal
- Molecular Metabolism
- Published
- 2025-03-27
- DOI
- https://doi.org/10.1016/j.molmet.2025.102124
- Citations
- 13
- Primary Topic
- Diabetes Treatment and Management
- Type
- article
- Field-Weighted Citation Impact
- 16.83