Wegovy, Ozempic may ease liver scarring in cases of advanced fatty liver disease

A phase II trial has found that semaglutide, the glucagon‑like peptide‑1 medicine widely used for diabetes and obesity, may also help to reduce liver scarring in patients with advanced MASH, including those with early cirrhosis

Researchers at the University of California San Diego School of Medicine (UCSD) have reported results from a large international clinical trial to show that semaglutide, a medicine in the glucagon‑like peptide‑1 (GLP‑1) receptor agonist class of drugs that is widely used to treat diabetes and obesity, may also help to reduce liver scarring in patients with advanced fatty liver disease, including those who have already developed early‑stage cirrhosis.

The findings address a significant unmet need for people with metabolic dysfunction‑associated steatohepatitis (MASH), a serious form of fatty liver disease that can progress to cirrhosis, liver failure and the need for a transplant. Semaglutide is widely marketed under the names Wegovy and Ozempic.

“This is the first clinical trial to demonstrate that semaglutide may improve liver fibrosis in patients with advanced MASH, including those with compensated cirrhosis,” said Dr. Rohit Loomba, the study’s senior author, a gastroenterologist and hepatologist at UCSD Health and chief of the Division of Gastroenterology and Hepatology at UCSD School of Medicine.

“The results with semaglutide alone are encouraging and suggest a potential novel treatment option for a group of patients who previously had very few,” he said.

The phase II trial followed around 700 adults with biopsy‑confirmed MASH and moderate to advanced liver scarring, including participants who had already developed early cirrhosis. Researchers set out to establish whether combining zalfermin – an experimental medicine designed to improve the body’s metabolism – with the GLP‑1 receptor agonist semaglutide could reverse liver fibrosis more effectively than either treatment alone.

Zalfermin is a novel, long‑acting analogue of fibroblast growth factor 21 (FGF21) – a hormone produced mainly by the liver that helps to regulate insulin, fat metabolism and body weight – it is being developed by Novo Nordisk and remains in clinical trials for MASH.

While the combination therapy did not outperform a placebo, semaglutide on its own showed a statistically significant improvement in liver scarring, without a worsening of the underlying liver inflammation, even among patients with the most advanced levels of disease.

MASH affects millions of people worldwide and has become one of the fastest‑growing causes of liver failure and liver transplantation. As the disease progresses, scar tissue builds up in the liver and eventually impairs its ability to function.

Until now, patients with cirrhosis caused by MASH have often been excluded from clinical trials and have had limited treatment options, a fact that makes the findings particularly noteworthy.

Loomba is also the founding director of the UCSD MASLD Research Center where his multidisciplinary team carries out translational research across all aspects of metabolic dysfunction‑associated steatotic liver disease (MASLD).

The study also found that non‑invasive blood tests and imaging measures reflected treatment‑related improvements more clearly than liver biopsies did. This could eventually help to reduce reliance on biopsies – which are invasive and difficult to repeat – and could make it easier for clinicians to monitor patients over time.

The researchers have emphasised that larger clinical trials focused specifically on patients with cirrhosis are needed to confirm these results. They have also noted that other drugs in the same class as zalfermin, designed slightly differently, may still hold promise and deserve further study.

“These findings strengthen the need to continue studying semaglutide and other metabolic therapies in advanced liver disease. Our goal is to move the field toward effective, accessible treatments that can slow or even reverse liver damage before patients reach liver failure,” Loomba said.

For further reading please visit: 10.1016/S2468-1253(26)00123-8