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Semaglutide Shows Promise in Treating Severe Fatty Liver Disease, Landmark Trial Finds

A global Phase 3 clinical trial involving more than 800 participants found that semaglutide improved key markers of the disease, including inflammation and liver fibrosis. The study, published in the New England Journal of Medicine, may set the stage for regulatory approval of semaglutide for MASH treatment.

• By Pooja Chaturvedi Sah
• New Delhi
• May 05, 2025

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Semaglutide, a drug currently used to manage diabetes and obesity under the brand names Ozempic and Wegovy, has shown significant results in treating a serious liver condition known as metabolic dysfunction-associated steatohepatitis (MASH).

A global Phase 3 clinical trial involving more than 800 participants found that semaglutide improved key markers of the disease, including inflammation and liver fibrosis. The study, published in the New England Journal of Medicine, may set the stage for regulatory approval of semaglutide for MASH treatment.

Trial Design and Results

The ESSENCE trial, funded by Novo Nordisk and led by researchers in the U.S. and U.K., assigned participants with confirmed MASH to receive either a weekly 2.4 mg injection of semaglutide or a placebo over 72 weeks. All participants were also provided with lifestyle counseling.

By the end of the trial, 62.9% of participants receiving semaglutide showed resolution of liver inflammation, compared to 34.3% in the placebo group. Additionally, 36.8% of semaglutide users had an improvement in liver fibrosis, versus 22.4% of those on placebo. A combined reduction in both inflammation and fibrosis was observed in 32.7% of the semaglutide group and 16.1% of the placebo group.

Participants on semaglutide also recorded an average weight loss of 10%. Reported side effects were consistent with previous trials and mainly included gastrointestinal symptoms such as nausea, vomiting, and diarrhea.

Disease Background

MASH is the most advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD). The condition involves fat accumulation in the liver, leading to inflammation and scarring.

MASLD is considered the most prevalent liver disease globally, affecting roughly one in four adults in the U.S. An estimated 6.5% of U.S. adults develop MASH, which increases the risk of liver failure and hepatocellular carcinoma.

Obesity and type 2 diabetes are major risk factors. Approximately 75% of people who are overweight and 90% of those with severe obesity have MASLD. Between one-third and two-thirds of individuals with type 2 diabetes are also affected.

Expert Opinions

“This trial will provide real hope for patients with MASH,” said Philip Newsome, director of the Roger Williams Institute of Liver Studies at King’s College London. “While these results must be treated with caution, the analysis shows semaglutide can be an effective tool to treat this advanced liver disease.”

Arun Sanyal, professor of medicine at Virginia Commonwealth University and co-lead investigator, stated, “The results from this study 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.”

He added, “If approved, this could offer an additional therapeutic option for patients with MASH and fibrosis. This is crucial given the strong link between MASH and cardiovascular, metabolic, and renal conditions, where semaglutide has already shown established health benefits.”

Comparison With Other Treatments

The U.S. Food and Drug Administration (FDA) approved the first drug for MASH, Rezdiffra, in 2023. Rezdiffra works by targeting a receptor that reduces liver fat without promoting weight loss. Experts say having multiple treatment options could help address varied patient responses and profiles.

Need for Further Research

Some researchers note that the trial does not account for the confounding effect of weight loss, a known factor in liver disease improvement. Studies show that losing 7–10% of body weight can reduce liver fat, and weight loss beyond 10% may reverse fibrosis, even without drug intervention.

The ESSENCE trial will continue for up to five years to evaluate the long-term effects of semaglutide on liver disease progression.

“By treating both liver disease and its metabolic causes, semaglutide offers a promising new approach for millions of patients,” said Sanyal.