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Semaglutide has already changed treatment for type 2 diabetes and obesity. Now it is moving into a new area that has been very hard to treat: fatty liver disease that causes inflammation and scarring.
In August 2025, the FDA granted an accelerated approval for Wegovy (semaglutide 2.4 mg) to treat adults with metabolic dysfunction associated steatohepatitis, or MASH, who also have moderate to advanced liver fibrosis. MASH was previously known as NASH, or nonalcoholic steatohepatitis.
This makes Wegovy only the second drug ever approved for MASH and the first GLP-1 based treatment for this condition. Although the approval is based on interim data and the main study is still running, it represents a major step forward for people living with advanced fatty liver disease.
Below is what this means, how semaglutide works in the liver, and who might benefit.
What Is MASH and Why Does It Matter?
MASH is a form of fatty liver disease where fat buildup in the liver triggers ongoing inflammation and damage. Over time, this can cause fibrosis, which is the formation of scar tissue.
If fibrosis continues to progress, it can lead to:
• Cirrhosis
• Liver failure
• Increased risk of liver cancer
MASH is strongly linked with:
• Obesity
• Type 2 diabetes
• Metabolic syndrome
• High blood pressure and high cholesterol
For years, lifestyle changes such as weight loss, improved diet, and exercise have been the main treatment. These are still important, but they can be difficult to sustain and do not always fully stop disease progression. That is why medications like semaglutide are gaining so much attention.
Wegovy’s Accelerated Approval for MASH
The FDA granted Wegovy accelerated approval for adults with MASH and moderate to advanced fibrosis (stages F2 to F3) who do not yet have cirrhosis. Accelerated approval means the decision is based on strong early evidence using surrogate markers such as liver inflammation and scarring on biopsy, rather than long term outcomes like survival.
The approval relies on data from a large, ongoing phase 3 study often referred to as the ESSENCE trial. The trial is still in progress, but 72 week results showed meaningful improvements in liver health compared to placebo. The study is expected to continue for several years to confirm long term benefits.
What the ESSENCE Trial Showed
In the ESSENCE trial, adults with biopsy confirmed MASH and liver fibrosis received either weekly semaglutide or placebo for 72 weeks. Researchers looked at how often participants showed improvement in liver inflammation and scarring.
Key findings included:
• More people on semaglutide had resolution of MASH without worsening fibrosis
• More people on semaglutide had an improvement in fibrosis stage without worsening inflammation
• Participants on semaglutide lost substantially more body weight than those on placebo
• Markers of liver injury and inflammation improved
• Side effects were mostly gastrointestinal and led to few treatment discontinuations
The trial is planned to continue to 240 weeks. Later analyses will help determine whether these early improvements translate into fewer cases of cirrhosis, liver failure, liver cancer, and liver related deaths.
Earlier Evidence for Semaglutide in Fatty Liver Disease
The ESSENCE results did not appear out of nowhere. Earlier studies had already suggested that semaglutide could help reduce fat and inflammation in the liver.
Phase 2 trials found that semaglutide:
• Reduced liver fat content on imaging
• Increased the proportion of patients with resolution of steatohepatitis on biopsy
• Improved metabolic markers such as A1C, cholesterol, and triglycerides
Meta analyses combining multiple smaller studies also showed that semaglutide lowers liver fat and reduces liver enzyme levels, both of which signal better liver health.
Taken together, these data support the idea that semaglutide acts not only on weight and blood sugar, but on the liver as an organ.
How Semaglutide Helps in MASH and Fibrosis
Semaglutide is a GLP-1 receptor agonist. It mimics a natural hormone that affects appetite, insulin release, and digestion. In MASH, its benefits appear to come from both direct and indirect effects.
Major mechanisms include:
• Significant weight loss, which reduces fat stored in the liver
• Improved insulin sensitivity, which reduces fat buildup and inflammation
• Better blood sugar and triglyceride control
In the liver itself, semaglutide appears to:
• Reduce inflammatory activity
• Help prevent further scar tissue formation
• Support partial reversal of existing fibrosis in some patients
Researchers believe that by improving overall metabolic health and reducing liver fat, semaglutide removes much of the ongoing stress that drives inflammation and scarring.
Benefits Beyond the Liver
MASH rarely exists alone. Most patients have other metabolic conditions that also respond well to semaglutide.
Potential additional benefits include:
• Lower A1C in people with type 2 diabetes
• Reduced cardiovascular risk in patients with established heart disease
• Lower blood pressure and improved cholesterol profiles
Because people with MASH have a higher risk of cardiovascular events, these extra benefits are particularly important.
Common Side Effects of Semaglutide
The side effect profile of Wegovy for MASH is similar to what has been seen in obesity and diabetes trials.
The most frequent side effects are gastrointestinal:
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal discomfort or bloating
These are usually most noticeable when treatment begins or when the dose is increased. They often improve with time.
To reduce side effects, clinicians typically:
• Start at a low dose
• Increase the dose slowly over several weeks
• Recommend smaller meals and slower eating
In trials for liver disease, only a small proportion of participants stopped the medication because of side effects, suggesting that most people can tolerate it with proper dose titration.
Who Is a Candidate for Wegovy in MASH?
Wegovy’s MASH indication is specific. It is approved for adults who:
• Have biopsy confirmed MASH
• Have moderate to advanced fibrosis (F2 to F3)
• Do not yet have cirrhosis
It is generally considered when:
• Lifestyle measures alone have not sufficiently improved liver disease
• There is a need to address both metabolic risk factors and liver damage
It is not appropriate for people who:
• Have decompensated cirrhosis
• Have a history of medullary thyroid carcinoma or MEN2
• Have a history of certain serious gastrointestinal conditions or pancreatitis
• Are pregnant, planning pregnancy soon, or breastfeeding
Because MASH often coexists with diabetes, obesity, and other conditions, treatment decisions need to be personalized and made with a specialist familiar with both liver and metabolic disease.
How Wegovy Fits Into Overall MASH Treatment
Even with an effective medication, foundational lifestyle measures remain important. Wegovy is meant to be part of a comprehensive plan rather than a replacement for healthy habits.
Most treatment plans include:
• Gradual, sustained weight loss
• A nutrient dense eating pattern
• Regular physical activity
• Control of blood pressure, cholesterol, and blood sugar
• Avoidance of heavy alcohol use
Wegovy can make it easier to achieve and maintain weight loss, which in turn lowers liver fat and inflammation. However, long term success still depends on maintaining supportive lifestyle patterns.
The Bottom Line
The approval of Wegovy for MASH with liver fibrosis represents an important advance for people living with advanced fatty liver disease. Early trial results show that semaglutide can reduce liver inflammation, improve fibrosis scores, and deliver significant metabolic benefits at the same time.
The ESSENCE trial and other ongoing studies will clarify how well these improvements translate into long term protection against cirrhosis, liver failure, and cardiovascular events. For now, Wegovy offers a new and promising option for eligible adults with MASH, especially when used alongside lifestyle changes and close medical follow up.
If you have fatty liver disease, MASH, or liver fibrosis and are wondering whether Wegovy might be appropriate, it is important to talk with a liver specialist or metabolic clinician who can review your individual situation, test results, and overall health goals.
