University of California San Diego School of Medicine researchers led an international Phase 2 trial showing that semaglutide, a GLP-1 drug, improved liver fibrosis in patients with advanced metabolic dysfunction-associated steatohepatitis MASH , including early cirrhosis. The combination with…
Researchers at the University of California San Diego School of Medicine have reported results from a large international clinical trial. The study indicates that semaglutide, a medication belonging to 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. This includes individuals who have already developed early-stage cirrhosis.
The study results were published in the July 15, 2026, online edition of The Lancet Gastroenterology & Hepatology. They address a major unmet medical need for people with metabolic dysfunction-associated steatohepatitis, or MASH. MASH is a serious form of fatty liver disease that can progress to cirrhosis, liver failure, and the need for liver transplantation.
Rohit Loomba, MD, serves as the senior author of the study. He is a gastroenterologist and hepatologist at UC San Diego Health and chief of the Division of Gastroenterology and Hepatology at UC San Diego School of Medicine. Loomba stated, "This is the first clinical trial to demonstrate that semaglutide may improve liver fibrosis in patients with advanced MASH, including those with compensated cirrhosis." He added that the results with semaglutide alone are encouraging and suggest a potential new treatment option for a group of patients who previously had very few options.
The Phase 2 clinical trial followed approximately 700 adults. All participants had biopsy-confirmed MASH and displayed moderate to advanced liver scarring. The study group included individuals who had already developed early cirrhosis. Researchers designed the trial to test whether combining zalfermin, an experimental medicine intended to improve the body's metabolism, with a GLP-1 receptor agonist could reverse liver fibrosis more effectively than either treatment given alone.
Contrary to expectations, the combination therapy did not outperform the placebo. However, the GLP-1 drug semaglutide on its own showed a statistically significant improvement in liver scarring. This benefit occurred without worsening underlying liver inflammation, even among patients with the most advanced stage of 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 accumulates in the liver, eventually impairing its ability to function properly. Until now, patients with cirrhosis caused by MASH have often been excluded from clinical trials and have had very limited treatment options. This makes the current findings particularly noteworthy.
Loomba is also the founding director of the UC San Diego MASLD Research Center. His multidisciplinary team focuses on performing leading-edge translational research in all aspects of metabolic dysfunction-associated steatotic liver disease MASLD .
The study also uncovered an important methodological finding. 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. It may also make it easier for clinicians to monitor patients over time without needing repeated tissue sampling.
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 with slightly different molecular characteristics, may still hold promise and deserve further investigation.
Loomba concluded, "These findings strengthen the need to continue studying semaglutide and other metabolic therapies in advanced liver disease." He added, "Our goal is to move the field toward effective, accessible treatments that can slow or even reverse liver damage before patients reach liver failure."
The full reference for the study is: 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. Lancet Gastroenterol Hepatol. 2026:S2468125326001238. doi: 10.1016/S2468-1253 26 00123-8.
Peptides referenced: Semaglutide, GLP-1.
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