New research reveals that semaglutide significantly improves liver health in MASH patients.
A new study published in the New England Journal of Medicine reveals that semaglutide significantly improves outcomes for patients with a serious form of liver disease, benefiting approximately two-thirds of those treated.
The findings come from the ESSENCE phase 3 clinical trial, a placebo-controlled study evaluating semaglutide’s effects on individuals with Metabolic dysfunction-associated steatohepatitis (MASH), a progressive, potentially fatal liver condition. The trial, involving 253 sites across 37 countries, is the first regulatory-grade investigation to demonstrate the therapeutic potential of semaglutide for MASH.
The study was led by Professors Philip Newsome of King’s College London and Arun Sanyal of the VCU School of Medicine in the United States, and was funded by Novo Nordisk.
MASH is a more advanced stage of Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD). MASLD arises from the accumulation of excess fat in the liver and is strongly associated with obesity, type 2 diabetes, and cardiovascular disease. If left untreated, it can progress to inflammation, fibrosis, cirrhosis, and liver cancer.
While MASLD affects roughly 20% of the UK population, there are currently no approved medications specifically targeting this disease.
Why Semaglutide?
Researchers chose to investigate semaglutide as a potential treatment because this class of drug helps reduce fat and liver scarring for people with MASH. Previous smaller but positive studies by Professor Newsome, published in the Lancet and NEJM, had shown using semaglutide as a treatment for MASH would have benefit for these patients.
Between May 27, 2021 and April 18, 2023, 800 participants were randomly assigned to receive once-weekly injection of 2.4 milligrams of semaglutide or placebo, alongside lifestyle counselling. More than half of participants had type 2 diabetes and approximately three-quarters were living with obesity.
Results of the ESSENCE Trial
Results from the ESSENCE trials after 72 weeks of treatment found 62.9% of participants experienced a reduction in steatohepatitis (inflammation of the liver with fat accumulation in the liver) versus 34.3% for participants who took the placebo. The results also show 36.8% of the semaglutide group had improvements of their liver fibrosis versus 22.4% in the placebo group. Researchers also found other benefits. Those receiving semaglutide also saw improvements in liver enzymes and other blood measures of liver fibrosis, as well as 10.5% weight loss. Gastrointestinal adverse events were more common in the semaglutide group, such as nausea, diarrhea, constipation, and vomiting.
Professor Philip Newsome, Director of the Roger Williams Institute of Liver Studies at King’s College London, said: “I’ve been working with GLP-1 treatments for sixteen years and these results are hugely exciting. MASLD is a growing problem worldwide and this trial will provide real hope for patients with MASH. While these results must be treated with caution, the analysis shows semaglutide can be an effective tool to treat this advanced liver disease.”
The research team will recruit up to 1,200 participants from 37 countries for up to five years to gather data on semaglutide’s impact on long-term liver complications.
Reference: “Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis” by Arun J. Sanyal, Philip N. Newsome, Iris Kliers, Laura Harms Østergaard, Michelle T. Long, Mette Skalshøi Kjær, Anna M.G. Cali, Elisabetta Bugianesi, Mary E. Rinella, Michael Roden and Vlad Ratziu, 29 April 2025, New England Journal of Medicine.
DOI: 10.1056/NEJMoa2413258
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