In a significant advancement for liver disease management, the U.S. Food and Drug Administration (FDA) has approved Wegovy® (semaglutide) injection 2.4 mg as the first glucagon-like peptide-1 receptor agonist (GLP-1 RA) to treat adults with metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (stages F2 to F3), but not cirrhosis. This approval, announced by Novo Nordisk, marks a pivotal milestone in addressing a chronic condition that affects approximately 5% of the U.S. population and is a leading cause of liver-related complications worldwide.
What is MASH and Why Does This Matter?
Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH), is a severe form of fatty liver disease characterized by fat accumulation, inflammation, and progressive liver scarring (fibrosis). It impacts roughly one in three individuals with obesity or overweight globally, often remaining undiagnosed due to its asymptomatic early stages. If untreated, MASH can progress to cirrhosis, liver cancer, or the need for a liver transplant, making it a critical public health concern. In the U.S., MASH-related cirrhosis is the second most common reason for liver transplants.
The FDA’s approval of Wegovy® for MASH with moderate to advanced fibrosis offers hope to millions. This new indication, used alongside a reduced-calorie diet and increased physical activity, provides a novel treatment option for a disease with historically limited therapeutic solutions.
Clinical Evidence: The ESSENCE Trial
The FDA granted accelerated approval based on compelling results from Part 1 of the ESSENCE trial, a phase 3 study evaluating once-weekly Wegovy® 2.4 mg in adults with MASH and moderate to advanced liver fibrosis. The trial, involving 1,197 participants randomized 2:1 to receive Wegovy® or placebo, demonstrated significant improvements at 72 weeks:
- Resolution of Steatohepatitis: 63% of patients treated with Wegovy® achieved resolution of steatohepatitis without worsening liver fibrosis, compared to 34% on placebo (difference: 29%, 95% CI: 21–36).
- Improvement in Liver Fibrosis: 37% of Wegovy®-treated patients showed improved liver fibrosis without worsening steatohepatitis, compared to 22% on placebo (difference: 14%, 95% CI: 8–21).
- Combined Endpoint: 33% of patients on Wegovy® achieved both resolution of steatohepatitis and improved fibrosis, compared to 16% on placebo (difference: 17%, 95% CI: 10–23).
Notably, 83.5% of patients in the Wegovy® group maintained the target dose of 2.4 mg through Week 72, underscoring the treatment’s tolerability. Part 2 of the ESSENCE trial is ongoing, aiming to confirm whether Wegovy® reduces liver-related clinical events, such as progression to cirrhosis, over 240 weeks.
Expert Insights
“This approval represents a transformative step in managing MASH, a disease that can have devastating consequences if left unchecked,” said Dr. Arun Sanyal, Director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University. “The ESSENCE trial results highlight Wegovy’s potential to address both liver inflammation and scarring, offering a new tool to improve outcomes for patients with moderate to advanced fibrosis.”
Dave Moore, Executive Vice President of U.S. Operations at Novo Nordisk, emphasized the broader impact: “MASH has long been underrecognized and undertreated. This approval not only expands treatment options but also builds on Wegovy’s proven benefits across obesity, cardiovascular disease, and now liver health, reinforcing its role in managing complex chronic conditions.”
Broader Applications of Wegovy®
Initially approved in 2021 for weight management in adults with obesity or overweight with weight-related conditions, Wegovy® has since expanded its indications. In 2022, it was approved for adolescents aged 12 and older with obesity. In 2024, the FDA approved it to reduce major cardiovascular events (e.g., heart attack, stroke, or death) in adults with known heart disease and obesity or overweight. This latest approval for MASH further broadens Wegovy’s therapeutic reach, showcasing its versatility in addressing interconnected metabolic and liver conditions.
Global Regulatory Efforts
Beyond the U.S., Novo Nordisk is seeking approval for Wegovy® in MASH treatment in other regions. In February 2025, the company submitted an application to the European Medicines Agency (EMA), followed by a submission in Japan in May 2025. These efforts reflect a global commitment to addressing the unmet needs of the MASH community.
Safety Considerations
While Wegovy® offers significant benefits, it comes with important safety considerations. Patients should be aware of potential serious side effects, including:
- Thyroid Tumors: Wegovy® may increase the risk of thyroid tumors, including medullary thyroid carcinoma (MTC). It is contraindicated in patients with a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Pancreatitis: Severe abdominal pain, nausea, or vomiting may indicate pancreatitis, requiring immediate medical attention.
- Gallbladder Issues: Symptoms like upper abdominal pain, fever, or jaundice may signal gallbladder problems.
- Hypoglycemia: Particularly in patients with type 2 diabetes taking insulin or sulfonylureas, low blood sugar is a risk.
- Kidney Problems: Dehydration from nausea, vomiting, or diarrhea may lead to kidney issues.
- Allergic Reactions: Severe allergic reactions require immediate cessation and medical care.
- Mental Health: Patients should monitor for depression or suicidal thoughts and consult their healthcare provider if these occur.
Common side effects include nausea, diarrhea, vomiting, constipation, abdominal pain, headache, and fatigue. Patients should discuss all medical conditions and medications with their healthcare provider before starting Wegovy®.
What’s Next?
The approval of Wegovy® for MASH is a game-changer, offering a new option for a disease that affects millions yet often goes undetected until advanced stages. As research continues, including the ongoing ESSENCE trial, we anticipate further insights into Wegovy’s long-term benefits in preventing liver-related complications. For now, this approval empowers patients and healthcare providers to tackle MASH proactively, combining medication with lifestyle changes to improve liver health and overall well-being.
For more information, consult your healthcare provider or visit Novo Nordisk’s official resources.