GLP-1 shows promise for patients with advanced fatty liver disease, suggests study
Researchers at University of California San Diego School of Medicine have reported results from a large international clinical trial showing that semaglutide, a medication in the GLP-1 class of drugs widely used to treat diabetes and obesity, may help reduce liver scarring in patients with advanced fatty liver disease, including those with early-stage cirrhosis.
The study results, published in the July 15, 2026, online edition of The Lancet Gastroenterology & Hepatology, address a major unmet need for people with metabolic dysfunction–associated steatohepatitis (MASH), a serious form of fatty liver disease that can lead to cirrhosis, liver failure, and the need for transplantation.
“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 Rohit Loomba, MD, senior author of the study, gastroenterologist and hepatologist at UC San Diego Health and chief of the Division of Gastroenterology and Hepatology at UC San Diego School of Medicine. “The results with semaglutide alone are encouraging and suggest a potential new treatment option for a group of patients who previously had very few.”
The Phase II trial followed about 700 adults with biopsy-confirmed MASH and moderate to advanced liver scarring, including participants who had already developed early cirrhosis. Researchers tested whether combining zalfermin, an experimental medicine designed to improve the body’s metabolism, with GLP-1 receptor agonist, could reverse liver fibrosis more effectively than either treatment alone.
While the combination therapy did not outperform the placebo, GLP-1 on its own showed a statistically significant improvement in liver scarring without worsening underlying liver inflammation, even among patients with the most advanced disease.
MASH affects millions of people worldwide and is one of the fastest growing causes of liver failure and liver transplantation. As the disease progresses, scar tissue builds in the liver, eventually impairing 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, making the findings particularly noteworthy.
Loomba is also the founding director of the UC San Diego MASLD Research Center, where his multidisciplinary team is dedicated to performing leading-edge translational research in all aspects of MASLD.
The study also found that non-invasive blood tests and imaging measures reflected treatment-related improvements more clearly than liver biopsies. This could eventually help reduce reliance on biopsies, which are invasive and difficult to repeat, and make it easier for clinicians to monitor patients over time.
The researchers emphasize that larger clinical trials focused specifically on patients with cirrhosis are needed to confirm these results. They also note 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,” Loomba said. “Our goal is to move the field toward effective, accessible treatments that can slow or even reverse liver damage before patients reach liver failure.”
Reference:
Loomba R, George J, Castera L et al. Efficacy and safety of zalfermin co-administered with semaglutide in participants with fibrosis and cirrhosis due to metabolic dysfunction-associated steatohepatitis: a phase 2, dose-ranging, double-blind, randomised controlled trial, The Lancet Gastroenterology & Hepatology, DOI: 10.1016/S2468-1253(26)00123-8
