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Randomized controlled trial

ESSENCE: semaglutide 2.4 mg (Wegovy) for MASH liver disease

At 72 weeks, steatohepatitis resolved without worsening of fibrosis in 62.9% on semaglutide and 34.3% on placebo (difference of 28.7 percentage points; 95% CI, 21.1 to 36.2), and fibrosis was reduced without worsening of steatohepatitis in 36.8% versus 22.4% (difference of 14.4 percentage points; 95% CI, 7.5 to 21.3).

Sanyal AJ et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. New England Journal of Medicine, 2025. DOI: 10.1056/NEJMoa2413258

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Key facts

Drug
semaglutide
Design
Randomized controlled trial
Participants
800
Duration
72 weeks
Funding
Novo Nordisk
Registry
NCT04822181
Population
1,197 patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and stage 2 or 3 liver fibrosis, randomized 2:1 to semaglutide 2.4 mg once weekly or placebo for 240 weeks; this paper is the planned interim analysis at 72 weeks in the first 800 (534 on semaglutide and 266 on placebo).
Primary outcome
Two primary objectives of the first part, assessed on liver biopsy at 72 weeks: resolution of steatohepatitis without worsening of fibrosis, and reduction in fibrosis without worsening of steatohepatitis.

What it found

Mean weight loss, % of starting weight · 72 weeks
  • Semaglutide 2.4 mg weekly−10.5%
  • Placebo−2.0%

Difference: −8.5 points vs placebo (95% CI, −9.6 to −7.4).

Figures from the paperSee the results in a chart

At 72 weeks, steatohepatitis resolved without worsening of fibrosis in 62.9% on semaglutide and 34.3% on placebo (difference of 28.7 percentage points; 95% CI, 21.1 to 36.2), and fibrosis was reduced without worsening of steatohepatitis in 36.8% versus 22.4% (difference of 14.4 percentage points; 95% CI, 7.5 to 21.3). Both happened together in 32.7% versus 16.1% (difference of 16.5 percentage points; 95% CI, 10.2 to 22.8). Weight changed by −10.5% with semaglutide and −2.0% with placebo (difference of −8.5 percentage points; 95% CI, −9.6 to −7.4). Bodily pain scores did not differ between the groups, and digestive adverse events were more common with semaglutide.

Limitations

Funded by Novo Nordisk. It is an interim analysis of an ongoing trial: it is not yet known whether semaglutide reduces cirrhosis or other liver events, which according to the registry are the objective of the second part, at 240 weeks. The results are based on changes in the biopsy, an intermediate marker, not on symptoms or clinical events. It only included people with moderate or advanced fibrosis (stages 2 and 3), not with cirrhosis.

What it means for you

In people with MASH, the inflammatory form of fatty liver disease, and moderate or advanced fibrosis, steatohepatitis resolved without worsening fibrosis in 62.9% on weekly semaglutide 2.4 mg (the Wegovy dose), compared with 34.3% on placebo, according to the biopsy at 72 weeks. It is not yet known whether it prevents cirrhosis; the second part of the trial will tell. If you have fatty liver disease, your doctor or hepatologist can explain your options.

Further reading

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Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. New England Journal of Medicine.Sanyal AJ, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025;392(21):2089-2099.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 40305708 (abstract).accessed .
  3. ClinicalTrials.gov (National Library of Medicine).ClinicalTrials.gov record NCT04822181 (part 1 and part 2 primary outcomes).accessed .