Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of fatty liver disease that can result in serious health complications if left untreated. Globally, about one in three individuals with overweight or obesity are affected by MASH, and in the United States, approximately one in twenty people live with the condition. Excess fat accumulation in the liver can cause inflammation and scarring, with around 20% of MASH cases progressing to cirrhosis. In fact, MASH is among the leading causes of cirrhosis in U.S. adults and is the second most common indication for liver transplantation.
In a major advancement, the U.S. Food and Drug Administration (FDA) has approved a new indication for Wegovy® (semaglutide) injection 2.4 mg. Wegovy® is now the first and only glucagon-like peptide-1 receptor agonist (GLP-1 RA) FDA-approved to treat adults with MASH with moderate to advanced liver scarring (fibrosis) without cirrhosis, under a reduced-calorie diet and increased physical activity. The approval is based on evidence of improvement in both MASH and liver fibrosis, though confirmatory studies are ongoing.
This decision was made after evidence from the phase 3 ESSENCE trial, which examined the efficacy of once-weekly Wegovy® 2.4 mg injections in adults with MASH and stage F2–F3 fibrosis. There was a total of 534 participants on Wegovy® and 266 with a placebo. At Week 72, 63% of participants on Wegovy® achieved resolution of steatohepatitis (with no worsening of fibrosis) versus 34% on placebo, representing a statistically significant 29-point higher response rate (95% CI, 21–36).
For the second primary endpoint, 37% of patients on Wegovy® showed fibrosis improvement without deterioration in steatosis, and 22% of patients in the placebo group, for a significant difference of 14 (95% CI, 8;21). A secondary endpoint confirmed that 33% of patients taking Wegovy® had resolution of steatosis and improvement of fibrosis as compared to 16% of patients on placebo, with a significant difference of 17 (95% CI, 10;23). Importantly, 83.5% of patients treated with semaglutide maintained the target dose of 2.4 mg through Week 72.
Commenting on the approval, Dr. Arun Sanyal, Director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, said, “Today’s FDA decision underscores the progress we continue to make in understanding and treating patients with MASH. When left untreated, MASH can lead to significant and potentially fatal complications. The clinical results seen in ESSENCE support the potential of this approach.”
Dave Moore, executive vice president of U.S. Operations at Novo Nordisk, noted, “This milestone is significant. For too long, this disease has been invisible, underdiagnosed, and frequently undertreated. The conditional approval of Wegovy® for adults with noncirrhotic MASH is an important step.”
Wegovy® first received FDA approval in 2021 for the treatment of weight management for adults with obesity or overweight and associated health concerns. In 2022, its label was extended to treat children aged 12 years and older with obesity, and in 2024, it was approved to reduce the risk for major cardiovascular events among adults with obesity or overweight and known heart disease. With its latest accelerated approval, Wegovy® is now available for adults with MASH and moderate to advanced fibrosis, offering hope for patients who are at risk for serious liver-related complications.
References: Novo nordisk. Wegovy® approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. Published Aug 15, 2025. Accessed August 18, 2025. Wegovy® approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis
