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Semaglutide in metabolic dysfunction–associated steatohepatitis (MASH)

Authoring team

Metabolic dysfunction–associated steatohepatitis (MASH)

  • was formerly called non–alcohol-related steatohepatitis, is a severe form of metabolic dysfunction–associated steatotic liver disease (MASLD; formerly, nonalcoholic fatty liver disease), characterized by steatosis, hepatocyte damage, and inflammation
  • steatohepatitis promotes liver fibrosis, progression to cirrhosis, and hepatocellular carcinoma
  • advanced fibrosis (stage 3 or higher) significantly increases liver-related and all-cause mortality

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used in the management of obesity and type 2 diabetes:

  • in an interim analysis of ESSENCE study (n=800), semaglutide associated with higher steatohepatitis resolution without worsening of liver fibrosis (difference vs placebo: 28.7% [95% CI 21.1-36.2]) & reduction in liver fibrosis without worsening steatohepatitis (14.4% [7.5-21.3%]
    • the study authors concluded that in patients with MASH and moderate or advanced liver fibrosis, once-weekly semaglutide at a dose of 2.4 mg improved liver histologic results

Reference:

  1. Sanyal AJ et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis. NEJM April 30th 2025.

 

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