In a randomised trial, semaglutide had favourable effects on steatohepatitis and fibrosis in liver biopsies.

Observational studies and small clinical trials have suggested that glucagon-like pepide-1 (GLP-1) agonists have favourable effects in patients with metabolic dysfunction-associated steatohepatitis (MASH). In an industry-sponsored, phase 3, multicentre, randomised US trial (the ESSENCE study), researchers now provide additional evidence in 800 patients (mean age, 56 years) with liver biopsy-proven MASH and stage 2 or 3 fibrosis.

At baseline, mean body mass index (BMI) was 35 kg/m², and 56% of ­patients had type 2 diabetes. Patients received semaglutide (titrated to 2.4 mg) or placebo once weekly, and liver biopsies were repeated at 72 weeks. Semaglutide recipients were significantly more likely than placebo recipients to have resolution of steatohepatitis without worsening fibrosis (63% vs 34%) and reduction in fibrosis without worsening of steatohepatitis (37% vs 22%). As expected, weight loss was greater with semaglutide than with placebo (10% vs 2% reduction in body weight).

Comment: Semaglutide is not specifically US FDA-approved for treating patients with MASH. However, many of these patients also have obesity or diabetes and thus would be candidates for GLP-1 agonist treatment on those grounds. This study ultimately will include about 1200 patients who will be followed for five years to examine a clinical (and not simply histological) endpoint – cirrhosis-free survival.

Allan S. Brett, MD, Clinical Professor of Medicine, University of Colorado School of Medicine, Aurora, USA.

Sanyal AJ, et al. Phase 3 trial of semaglutide in metabolic dysfunction–associated steatohepatitis. N Engl J Med 2025 Apr 30; e-pub (https://doi.org/10.1056/ NEJMoa2413258).

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Gastroenterology.