By AJ Hostetler 

An international study led by the director of Virginia Commonwealth University’s liver institute suggests that the substance in Ozempic and Wegovy can halt and even reverse a common liver disease that affects millions worldwide. 

Led by Arun Sanyal, M.D., of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, and Philip Newsome, Ph.D., of King’s College London, researchers are exploring the potential of semaglutide to treat people with metabolic dysfunction-associated steatohepatitis, or MASH. They reported their results from a phase 3 clinical trial in this week’s New England Journal of Medicine. 

“The results from this landmark study across 37 countries provide strong evidence that semaglutide can help patients with MASH by not only improving liver health, but also addressing the underlying metabolic issues that contribute to the disease,” said Sanyal, who is the lead author on the new paper and is also a professor of medicine at the VCU School of Medicine. 

An estimated 15 million Americans have the liver disease MASH, which occurs when fat builds up in the liver, leading to inflammation and scarring. Currently, there is only one FDA-approved treatment available, increasing the urgency for effective therapeutic options. 

“If approved, this could offer an additional therapeutic option for patients with MASH and fibrosis,” Sanyal added. “This is crucial, given the strong link between MASH and cardiovascular, metabolic, and renal conditions, where semaglutide has already shown established health benefits.” 

MASH is closely linked to metabolic risk factors like obesity, type 2 diabetes, and high blood pressure. Over time, MASH can lead to liver fibrosis, cirrhosis, and even liver failure that requires a liver transplant, making it a major public health concern.  

Of the 800 participants in the “Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis” (ESSENCE) trial, 534 were assigned to take semaglutide and 266 were in a placebo group:  

• About 63% semaglutide users experienced a reduction in liver inflammation without worsening scarring, compared to only 34% of the placebo group.  
• Almost 37% of those on semaglutide showed less liver scarring, compared to nearly 23% in the placebo group.  
• About a third of semaglutide users achieved both inflammation reduction and scarring improvement, more than double compared to those taking the placebo. 
• The drug also helped participants with weight loss, improved liver markers, and boosted overall heart health – with no major differences in serious side effects compared to those not taking it. 

The ultimate goal for researchers in the ESSENCE trial is to find the right balance of semaglutide to resolve the damage caused by the fat buildup in the liver (steatohepatitis) while at the same time improve the scarring (fibrosis). Both are crucial for improving liver health in patients with MASH. 

Semaglutide is a GLP-1 receptor agonist medication. Wegovy and Ozempic are brand names for semaglutide and are approved to promote weight loss, improve blood sugar control, and enhance metabolic health. Sanyal and other researchers are studying several GLP-1 receptor agonists and related drugs as potential treatments that might help halt, improve or even reverse the damage caused by MASH. 

“The ESSENCE data may represent key findings for patients in the treatment of MASH, which is estimated to affect about one in 20 adults in the U.S.,” Sanyal said. “By treating both liver disease and its metabolic causes, semaglutide offers a promising new approach for millions of patients.” 

The clinical trial involved participants with moderate to advanced liver scarring who were treated for 72 weeks with either 2.4 milligrams weekly injections of semaglutide or a placebo. Most participants tolerated semaglutide well. Nearly 90% of participants remained on the medication after 72 weeks. The most common side effects were mild digestive issues, such as nausea.  

In the second part of this clinical trial, researchers led by Sanyal will follow nearly 1,200 participants from 37 countries for up to five years to gather data on semaglutide’s impact on long-term liver complications. 

Semaglutide, manufactured by Novo Nordisk, belongs to a class of drugs called GLP-1 receptor agonists. Ozempic and Wegovy are brand names for semaglutide and are approved by the U.S. Food and Drug Administration for different conditions. 

Semaglutide is not approved to treat MASH in the U.S. Pharmaceutical maker Novo Nordisk has said it plans to seek regulatory approval for its use in treating liver disease sometime this year. 

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