SAN DIEGO — Researchers at the University of California San Diego School of Medicine reported Thursday that semaglutide, a widely used GLP-1 medication, significantly improved liver scarring in patients with advanced fatty liver disease, including those with early cirrhosis, according to results from a large international Phase II trial published in The Lancet Gastroenterology & Hepatology.
The findings mark the first clinical trial evidence that semaglutide alone can reduce fibrosis in people with metabolic dysfunction-associated steatohepatitis (MASH) who already have moderate to advanced scarring or compensated cirrhosis—a group long excluded from many studies and left with few treatment options. While a combination with an experimental metabolic drug failed to outperform placebo, the GLP-1 results offer a potential new path for millions of patients at high risk of liver failure and transplantation, researchers said, though larger trials focused on cirrhosis are still needed.
Fibrosis is the excessive accumulation of fibrous connective tissue, primarily collagen, in an organ or tissue. It is essentially an overactive healing response where the body produces permanent scar tissue instead of normally repairing itself, which ultimately stiffens organs and impairs their function
“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.”
MASH, or metabolic dysfunction-associated steatohepatitis, is the more serious form of fatty liver disease. In simple fatty liver (now called metabolic dysfunction-associated steatotic liver disease, or MASLD), fat builds up in the liver but causes little or no inflammation or damage. In MASH, the fat is accompanied by inflammation and liver-cell injury that can lead to progressive scarring (fibrosis), cirrhosis, liver failure, and the need for a transplant.
GLP-1 receptor agonists are medications that mimic a natural gut hormone called glucagon-like peptide-1. They help the body release insulin when blood sugar is high, slow digestion, and reduce appetite. Originally developed for type 2 diabetes, several drugs in this class—including semaglutide (sold as Ozempic for diabetes and Wegovy for weight management)—are now also widely prescribed for chronic weight loss and, in some cases, to lower cardiovascular risk.
Semaglutide is believed to help the liver mainly through its broader metabolic effects. By promoting significant weight loss, improving insulin sensitivity, and reducing overall fat accumulation in the body, it can decrease the amount of fat stored in the liver. These changes may ease inflammation and slow the buildup of scar tissue. Researchers are still studying whether the drug also has more direct effects on liver cells or fibrosis pathways, but the primary benefits observed so far appear linked to its impact on weight and metabolism.
Patients with cirrhosis caused by MASH have long been excluded from most clinical trials of experimental liver drugs, largely because of safety concerns and the complexity of advanced disease. Impaired liver function can change how medications are processed, raising the risk of side effects or complications. As a result, research has focused mainly on earlier stages of fatty liver disease, leaving people who already have significant scarring with limited proven treatment options beyond lifestyle changes, managing complications, and, in severe cases, evaluation for transplant.
