Modulation of metabolic, inflammatory and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease strongly associated with cardiometabolic risk factors. Semaglutide, a glucagon-like peptide-1 receptor agonist, improves liver histology in MASH, but the underlying signals and pathways driving semaglutide-induced MASH resolution are not well understood. Here we show that, in two preclinical MASH models, semaglutide improved histological markers of fibrosis and inflammation and reduced hepatic expression of fibrosis-related and inflammation-related gene pathways. Aptamer-based proteomic analyses of serum samples from patients with MASH in a clinical trial identified 72 proteins significantly associated with MASH resolution and…

• BS
  Bristol-Myers Squibb
• EL
  Eli Lilly and Company
• P
  Pfizer
• A
  AstraZeneca
• G
  GlaxoSmithKline
• SU
  Siemens USA
• GS
  Gilead Sciences
• M
  Medpace
• AP
  Arrowhead Pharmaceuticals
• NI
  National Institute for Health and Care Research
• NU
  Newcastle University
• EC
  European Commission
• NN
  Novo Nordisk
• S
  Shionogi
• G
  Genentech
• NN
  NIHR Newcastle Biomedical Research Centre