1813-P: Coadministration of a GLP-1/Glucagon Receptor Agonist with an FXR Agonist and ACC Inhibitor Reverses Nonalcoholic Steatohepatitis (NASH) in Diet-Induced and Biopsy-Confirmed Mice
| Autor: | Michael Feigh, Jenny Norlin, James L. Trevaskis, Nora E. Zois, Diego A. Miranda, Markus Latta, Jamie G. Bates, Sanne Skovgård Veidal |
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| Rok vydání: | 2020 |
| Předmět: |
Nonalcoholic steatohepatitis
Agonist medicine.medical_specialty medicine.diagnostic_test medicine.drug_class business.industry Endocrinology Diabetes and Metabolism Fibrosis stage Body weight Endocrinology Hepatic lipid Internal medicine Biopsy Internal Medicine medicine Liver triglyceride business Glucagon receptor |
| Zdroj: | Diabetes. 69 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db20-1813-p |
| Popis: | Combination approaches for the treatment of NASH are being actively pursued. We examined the effects of administration of a dual GLP-1 and glucagon receptor agonist (GLP-1:GCG, 0.015 mg/kg, s.c., q.d.) alone and combined with an FXR agonist (cilofexor, CILO; 30 mg/kg) and/or an acetyl-CoA carboxylase inhibitor (firsocostat analog, ACCi; 5 mg/kg, both p.o., q.d) on NASH endpoints in the AMLN diet-induced and biopsy-confirmed DIO-NASH mouse (n=15-16/group). After 12 weeks of treatment, GLP-1:GCG reduced body weight 15%, being slightly greater in the GLP-1:GCG + CILO group (22%). Liver triglyceride was reduced by GLP-1:GCG (by 76% vs. vehicle, p In conclusion, GLP-1:GCG effectively reduced hepatic lipid and the addition of an FXR agonist and ACC inhibitor further improved pre-to-post NAS and fibrosis stage in DIO-NASH mice, supporting development of combination approaches for NASH. Disclosure J.L. Trevaskis: Employee; Self; Gilead Sciences, Inc. J. Norlin: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. D.A. Miranda: None. J.G. Bates: Employee; Self; Gilead Sciences, Inc. N.E. Zois: Employee; Self; Gubra. S. Veidal: None. M. Feigh: None. M. Latta: Employee; Self; Novo Nordisk A/S. |
| Databáze: | OpenAIRE |
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