Ozempic Shows Promise in Treating a Severe Form of Liver Disease, Study Finds

Ozempic is effective in treating a severe form of liver disease that affects nearly 2 million Americans, according to a study published in The New England Journal of Medicine in April.

The research included 800 people with metabolic dysfunction-associated steatohepatitis (MASH), an advanced stage of metabolic dysfunction–associated steatotic liver disease (MASLD), which begins with fat buildup in the liver.

Unlike some liver conditions, MASH isn’t caused by alcohol consumption. Instead, it is associated with obesity, type 2 diabetes, and cardiovascular disease.

For the study, the MASH patients received weekly injections of either a placebo or semaglutide, a glucagon-like peptide-1 receptor agonist and the active ingredient in the popular drugs Wegovy and Ozempic. The medications, approved by the Food and Drug Administration to treat obesity and type 2 diabetes, are manufactured by the pharmaceutical company Novo Nordisk, which funded the research.

After 72 weeks, two out of three patients on semaglutide had significant improvements in fat accumulation and scarring in the liver. Not all people with MASH experience scarring, but once it occurs due to fat buildup and inflammation, the risk of life-threatening conditions like cirrhosis, liver cancer, and liver failure rises. MASH is a leading cause of liver transplants in the United States.

The new research is the first regulatory study—one designed to help inform FDA decision-making—to find that the drug could improve scarring, said Philip Newsome, PhD, director of Roger Williams Institute of Liver Studies at King’s College London and study co-author.

“If you can stop the scarring, you can stop progression of the disease,” Newsome told Health.

The study results are part one of the third phase of a randomized, double-blind clinical trial lasting 240 weeks. 

For the first 72 weeks, 534 participants received 2.4 mg of semaglutide weekly, while 266 had a placebo. 

Based on liver biopsy reports, 62.9% of those receiving semaglutide had a reduction in steatohepatitis—liver fat and inflammation—without worsening scarring, compared to 34% in the placebo group.

Furthermore, 33% of those in the semaglutide group saw their scarring improve without worsening steatohepatitis, whereas 22.4% in the placebo group did. Those receiving semaglutide also had more improvement in liver enzyme levels in comparison to those taking a placebo.

Notably, compared to the placebo group, those taking semaglutide had improved cardiometabolic factors considered drivers of MASH, such as blood sugar levels and insulin resistance. They lost an average of 10.5% of body weight. 

The study suggests that semaglutide could decrease scarring progression that leads to advanced-stage liver disease, Manal Abdelmalek, MD, a gastroenterologist and hepatologist at Mayo Clinic, told Health.

But “equally important,” she added, “the improvement in insulin resistance, weight loss, and glycemic control in patients with MASH provides a holistic therapeutic approach to treatment of both liver disease and associated cardiometabolic illnesses, which also impact morbidity and mortality in patients with MASH.” 

Researchers don’t fully understand why semaglutide may help treat MASH. But the lack of GLP-1 receptors in the liver suggests that the drug doesn’t work directly on the organ but instead has an indirect effect by lowering weight and blood sugar levels, said Abdelmalek.

That reduces the risk of fat accumulation in the liver, lessening the activity of “downstream” pathways that drive scarring, she added.

In keeping with previous research, gastrointestinal upset, including nausea, vomiting, and diarrhea, were the most common side effects reported by study participants. However, only 2.6% of the semaglutide group—and 3.3% of the placebo group—discontinued the trial due to the adverse impacts.

The study’s limitations included a lack of Black participants, as well as a paucity of data on participant alcohol use and changes in body composition. 

However, Newsome said the results build on “encouraging data” from phase two of the trial.

Currently, there are few treatment options for MASH, a “21st-century epidemic that was largely unrecognized until very recently,” Christos S. Mantzoros, MD, DSc, PhD, chief of endocrinology, diabetes and metabolism at the Boston VA Healthcare System, told Health.

In 2024, the FDA approved the first drug—resmetirom—to treat MASH with moderate to advanced scarring. Doctors may prescribe that medication alongside changes to lifestyle factors, such as diet and exercise.

However, Abdelmalek said more therapies are needed because the long-term benefits of resmetirom remain unknown. Additionally, lifestyle changes can be challenging for patients—and may not even reverse advanced scarring.

Experts are hopeful that semaglutide will prove to be an effective option in the MASH treatment toolkit.

“This study will be the first of many studies to come which will address [current] study limitations and lend further insights regarding semaglutide as a treatment for MASH,” Abdelmalek said.

With the possible addition of semaglutide and a “robust pipeline of emerging therapies in phase 3 clinical trials,” she continued, “the future for our patients with MASH and MASH-related cirrhosis is bright.”