Semaglutide, a glucagon-like peptide-1 receptor agonist, is a candidate for the treatment of metabolic dysfunction–associated steatohepatitis (MASH).
Methods: In this phase 3 trial, 1197 patients with biopsy-confirmed MASH and liver fibrosis (stage 2 or 3) were randomly assigned to weekly semaglutide 2.4 mg or placebo. Interim results at 72 weeks from the first 800 patients are reported. Primary goals were resolution of steatohepatitis without worsening fibrosis and improvement in fibrosis without worsening steatohepatitis.
Results: Semaglutide led to steatohepatitis resolution without fibrosis worsening in 62.9% of patients vs. 34.3% with placebo. Fibrosis improved without worsening steatohepatitis in 36.8% vs. 22.4%. Both outcomes occurred in 32.7% vs. 16.1%. Weight loss was greater with semaglutide (−10.5% vs. −2.0%). GI side effects were more common with semaglutide; pain scores were similar.
Conclusions: Semaglutide 2.4 mg weekly significantly improved liver histology in MASH patients with fibrosis.