Abstract | AIMS: Unimolecular peptides targeting the receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) ( GLP-1/GIP co-agonist) have been shown to outperform each single peptide in the treatment of obesity and cardiometabolic disease in preclinical and clinical trials. By combining physiological treatment endpoints with plasma proteomic profiling (PPP), we aimed to identify biomarkers to advance non-invasive metabolic monitoring of compound treatment success and exploration of ulterior treatment effects on an individual basis. MATERIALS AND METHODS: We performed metabolic phenotyping along with PPP in body weight-matched male and female diet-induced obese (DIO) mice treated for 21 days with phosphate-buffered saline, single GIP and GLP-1 mono-agonists, or a GLP-1/GIP co-agonist. RESULTS: CONCLUSIONS: We herein show that a recently developed unimolecular GLP-1/GIP co-agonist is more efficient in improving metabolic disease than either mono-agonist in both sexes. PPP led to the identification of a sex-independent protein panel with the potential to monitor non-invasively the treatment efficacies on metabolic function of this clinically advancing GLP-1/GIP co-agonist.
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Authors | Stephan Sachs, Lili Niu, Philipp Geyer, Sigrid Jall, Maximilian Kleinert, Annette Feuchtinger, Kerstin Stemmer, Markus Brielmeier, Brian Finan, Richard D DiMarchi, Matthias H Tschöp, Nicolai Wewer Albrechtsen, Matthias Mann, Timo D Müller, Susanna M Hofmann |
Journal | Diabetes, obesity & metabolism
(Diabetes Obes Metab)
Vol. 23
Issue 1
Pg. 195-207
(01 2021)
ISSN: 1463-1326 [Electronic] England |
PMID | 33001570
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. |
Chemical References |
- Glucagon-Like Peptide-1 Receptor
- Incretins
- Proteome
- Gastric Inhibitory Polypeptide
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Topics |
- Animals
- Diet
- Female
- Gastric Inhibitory Polypeptide
- Glucagon-Like Peptide-1 Receptor
- Incretins
- Male
- Mice
- Mice, Obese
- Obesity
(drug therapy)
- Proteome
- Proteomics
- Treatment Outcome
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