Semaglutide Becomes First Drug Approved for MASH

The US Food and Drug Administration (FDA) has granted accelerated approval for Wegovy® (semaglutide) as a treatment for adults with moderate to advanced metabolic dysfunction-associated steatohepatitis (MASH).

The decision follows the Phase 3 ESSENCE trial, conducted by Novo Nordisk, which found that semaglutide significantly improved liver fibrosis and steatohepatitis compared with placebo.

“Wegovy is now uniquely positioned as the first and only GLP-1 treatment approved for MASH, complementing the already proven weight loss, cardiovascular benefits and extensive body of evidence linked to semaglutide,” said Dr. Martin Holst Lange, executive vice president, chief scientific officer and head of Research and Development, at Novo Nordisk.

MASH and the unmet need for GLP-1 therapies

MASH is a progressive condition that develops in people who are overweight or living with obesity. In its early stages, it causes few or no symptoms, meaning many cases go undiagnosed until the disease has already advanced. Left untreated, MASH can progress to cirrhosis, liver cancer or in some cases, liver failure.

“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,” said Lange.

Despite this scale, no drug therapies have been approved to treat the condition. The standard recommendation has been lifestyle changes, such as adopting a lower-calorie diet and increasing physical activity. While these steps are important, they are often not enough to halt or reverse disease progression.

Recently, attention has turned to drugs known as GLP-1 receptor agonists, such as semaglutide. Since weight loss can have a positive effect on liver health, scientists questioned whether semaglutide could also directly benefit people living with MASH.

Novo Nordisk launched the Phase 3 ESSENCE trial to put this idea to the test. The study set out to determine whether semaglutide could improve scarring in the liver (fibrosis) and inflammation (steatohepatitis) in adults with moderate to advanced stages of the disease.

Wegovy shows liver benefits in ESSENCE trial

Novo Nordisk enrolled nearly 1,200 adults with MASH and moderate to advanced fibrosis (stages F2–F3). Participants were randomly assigned in a 2:1 ratio to receive either semaglutide or a placebo, in addition to the standard recommendations of reduced calorie intake and increased physical activity.

The study was designed in two parts. Part one focused on liver histology after 72 weeks, using biopsies to measure changes in scarring and inflammation. Part two, which is ongoing and expected to run until 2029, aims to determine whether semaglutide can reduce the risk of major liver-related clinical events, such as progression to cirrhosis or liver failure.

The findings from part one showed clear benefits for patients on semaglutide compared to those receiving a placebo. At week 72, 36.8% of people treated with semaglutide demonstrated an improvement in liver fibrosis without worsening of inflammation, compared with 22.4% in the placebo group. Likewise, 62.9% of people on semaglutide showed resolution of steatohepatitis without worsening of fibrosis, compared with 34.3% on placebo.

These improvements were statistically significant across both measures and occurred without trade-offs in disease progression elsewhere in the liver.

The FDA has granted accelerated approval of semaglutide for the treatment of MASH in adults with moderate to advanced fibrosis. This approval is conditional, requiring confirmation from part 2 of the ESSENCE trial before full approval is considered. Regulatory filings are also underway in the European Union and Japan.

Implications of FDA approval for MASH treatment

The FDA’s decision marks the first time a pharmacological option has been approved for MASH, addressing an urgent unmet need in liver disease care.

“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 Lange.

Beyond liver health, these findings contribute to a growing body of evidence that GLP-1–based drugs may have benefits well beyond weight loss and diabetes management. For researchers and clinicians, the approval reinforces the idea that these therapies could play a broader role in tackling metabolic diseases.

However, the accelerated approval pathway means that evidence is still interim: while part one of the ESSENCE trial demonstrated improvement in liver scarring and inflammation, it does not yet show whether semaglutide reduces the risk of serious outcomes such as cirrhosis, liver failure or liver cancer. Those answers will depend on the results of part two of the trial.

This article is a rework of a press release issued by Novo Nordisk. Material has been edited for length and content.