FDA Approves Semaglutide 2.4 mg for Treatment of MASH Without Cirrhosis

The US Food and Drug Administration (FDA) approved semaglutide 2.4 mg (Wegovy; Novo Nordisk) for the treatment of noncirrhotic metabolic dysfunction–associated steatohepatitis (MASH) in adults with moderate to advanced liver fibrosis (stages F2 to F3), in combination with a reduced-calorie diet and increased physical activity, according to a company news release.

The accelerated approval for semaglutide was based on part 1 of the phase 3 ESSENCE trial, which met its primary endpoints. At week 72, 36.8% of patients receiving semaglutide achieved improvement in liver fibrosis with no worsening of steatohepatitis compared with 22.4% receiving placebo. Resolution of steatohepatitis with no worsening of liver fibrosis occurred in 62.9% of patients in the semaglutide group compared with 34.3% in the placebo group.

“MASH represents a significant health burden, with one in three people with overweight or obesity worldwide affected. In the US alone, around 22 million people are estimated to live with MASH. With the approval of Wegovy for MASH, we provide a new treatment to people living with MASH that not only halts the disease activity but helps reverse the damage caused to the liver," said Martin Holst Lange, MD, executive vice president, chief scientific officer, and head of research and development at Novo Nordisk, in a news release.

MASH is a progressive metabolic liver disease that affects more than 250 million people globally, with prevalence expected to rise sharply by 2030. Individuals often have few symptoms in early stages, delaying diagnosis and increasing the risk for advanced liver disease, including hepatocellular carcinoma.

ESSENCE is a two-part, 240-week trial randomizing 1,200 adults with MASH and F2–F3 fibrosis to semaglutide 2.4 mg or placebo in addition to standard of care. Part 1 assessed histologic outcomes at 72 weeks; part 2 will evaluate whether semaglutide reduces the risk of liver-related clinical events, with results expected in 2029.

Wegovy was first approved in 2021 for chronic weight management in adults with obesity or overweight with weight-related comorbidities, and its indications have since expanded to include adolescents with obesity and cardiovascular risk reduction in certain adults with obesity or overweight.

Reference

Novo Nordisk A/S. Wegovy® approved in the US for the treatment of MASH [news release]. August 15, 2025. Accessed August 15, 2025. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=167078