Semaglutide is not only hugely effective for weight loss and diabetes but it has now been found effective for people who have developed liver disease, according to an international team of scientists.
In a phase 3 clinical trial involving 800 participants and lasting 72 weeks, a weekly dose of semaglutide was effective in almost two-thirds of patients at treating the serious form of fatty liver disease known as Metabolic Dysfunction-Associated Steatohepatitis (MASH).
“The results from this landmark study across 37 countries provide strong evidence that semaglutide can help patients with MASH by not only improving liver health, but also addressing the underlying metabolic issues that contribute to the disease,” said Arun Sanyal, a professor of medicine at Virginia Commonwealth University.
The research was published in the New England Journal of Medicine.
The participants were split into two groups. Of those given the semaglutide treatment, 62.9% saw improvements in their MASH, compared with 34.3% of the group given a placebo treatment instead.
Additionally, they found, liver fibrosis (scarring) – which happens as the liver tries to repair damage – was reduced in 36.8% of patients given the semaglutide treatment, compared with 22.4% given placebos.
Improvements in both MASH and fibrosis were seen in 32.7% of the participants on semaglutide, compared with 16.1% of the placebo group. It’s a comprehensive win for the drug, which is showing potential in many different areas of health.
That placebo effect is fairly typical, and often happens in trials: it’s thought to be a combination of the psychological boost of thinking you’re being treated, plus a tendency to live more healthily and carefully if you know you’re part of a study.
“If approved, this could offer an additional therapeutic option for patients with MASH and fibrosis,” said Sanyal.
“This is crucial, given the strong link between MASH and cardiovascular, metabolic, and renal conditions, where semaglutide has already shown established health benefits.”
Semaglutide, a GLP-1 (glucagon-like peptide-1) receptor agonist, essentially acts like the natural GLP-1 hormone to help regulate key metabolic processes – including reducing appetite and lowering blood sugar.
And while that makes it effective for treating obesity and diabetes, this boost in biological regulation seems to have plenty of other benefits too. When it comes to liver disease, the thinking is that the metabolism and anti-inflammatory improvements triggered by the drug help to treat some of the key drivers of MASH.
This clinical trial, funded by Novo Nordisk, is continuing, expanding to a larger group of people for a full five years to see if these initial improvements continue. With only one approved treatment available for MASH, new options are urgently needed.
“By treating both liver disease and its metabolic causes, semaglutide offers a promising new approach for millions of patients,” said Sanyal.
Study details
Phase 3 trial of semaglutide in metabolic dysfunction–associated steatohepatitis
Arun Sanyal, Philip Newsome, Iris Kliers et al.
Published in New England Journal of Medicine on 30 April 2025
Abstract
Background
Semaglutide, a glucagon-like peptide-1 receptor agonist, is a candidate for the treatment of metabolic dysfunction–associated steatohepatitis (MASH).
Methods
In this ongoing phase 3, multicentre, randomised, double-blind, placebo-controlled trial, we assigned 1197 patients with biopsy-defined MASH and fibrosis stage 2 or 3 in a 2:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. The results of a planned interim analysis conducted at week 72 involving the first 800 patients are reported here (part 1). The primary end points for part 1 were the resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.
Results
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% confidence interval [CI], 21.1 to 36.2; P<0.001). A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of the patients in the semaglutide group and in 22.4% of those in the placebo group (estimated difference, 14.4 percentage points; 95% CI, 7.5 to 21.3; P<0.001). Results for the three secondary outcomes that were included in the plan to adjust for multiple testing were as follows: combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% of the patients in the semaglutide group and in 16.1% of those in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2 to 22.8; P<0.001). The mean change in body weight was −10.5% with semaglutide and −2.0% with placebo (estimated difference, −8.5 percentage points; 95% CI, −9.6 to −7.4; P<0.001). Mean changes in bodily pain scores did not differ significantly between the two groups. Gastrointestinal adverse events were more common in the semaglutide group.
Conclusions
In patients with MASH and moderate or advanced liver fibrosis, once-weekly semaglutide at a dose of 2.4 mg improved liver histologic results.
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