Semaglutide Linked to NASH Resolution

By Kelly Young

Edited by Susan Sadoughi, MD, and André Sofair, MD, MPH

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is associated with higher odds of nonalcoholic steatohepatitis (NASH) resolution in patients with stage F2 or F3 fibrosis, according to a phase 2, industry-conducted study published in the New England Journal of Medicine and presented at the American Association for the Study of Liver Diseases' Liver Meeting.

Over 300 adults with biopsy-confirmed NASH were randomized to receive one of three doses of daily subcutaneous semaglutide or placebo for 72 weeks. For the primary outcome, researchers studied NASH resolution without worsening fibrosis; for the secondary outcome, an improvement of at least one fibrosis stage without exacerbating NASH.

Among those with stage F2 or F3 fibrosis, the primary outcome occurred more frequently in those who received semaglutide (59% in the highest-dose group vs. 17% in the placebo group). Semaglutide was not associated with an improvement of at least one fibrosis stage. Neoplasms were identified at a higher rate in semaglutide recipients without an organ-specific pattern.

The authors speculate that the drug's mechanism of action "may relate to indirect beneficial effects on weight and insulin resistance, as well as reductions in metabolic dysfunction, lipotoxic effects, and inflammation."