Triple Combination Therapy Of Glp-1 Receptor Agonist Semaglutide With An Fxr Agonist And Acc Inhibitor Reverses Non-Alcoholic Steatohepatitis (Nash) In Diet-Induced And Biopsy-Confirmed Mice.

Semaglutide (SEMA), FXR agonists and ACC inhibitors are under active clinical investigation for the treatment of NASH. Here, we explored whether the effects of SEMA (0.12 mg/kg, s.c., q.d.) on NASH endpoints could be enhanced by addition of an FXR agonist (cilofexor, CILO; 30 mg/kg) and/or an acetyl-CoA carboxylase inhibitor (firsocostat analogue, ACCi; 5 mg/kg, both p.o., q.d.) in the AMLN diet-induced and biopsy-confirmed DIO-NASH mouse (n=15-16/group). After 12 weeks of treatment, SEMA and triple therapy reduced body weight 18%, being slightly enhanced in the double combination of SEMA+CILO (21%). Liver triglyceride concentration was reduced by SEMA (by 38% vs. vehicle, p Disclosure 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. J.L. Trevaskis: Employee; Self; Gilead Sciences, Inc. M. Latta: Employee; Self; Novo Nordisk A/S.