Semaglutide (WEGOVY) for Metabolic Dysfunction-Associated Steatohepatitis

In August 2025 the Food and Drug Administration (FDA) granted accelerated approval to injectable semaglutide (WEGOVY) to treat metabolic dysfunction-associated steatohepatitis (MASH) in adults with moderate-to-advanced fibrosis (excessive scar tissue in the liver).[1]

MASH, formerly known as nonalcoholic steatohepatitis (NASH), is a nonalcoholic, chronic fatty liver disease that affects approximately 30% to 40% of the adult population globally, including about 60% to 70% of individuals with type 2 diabetes and 70% to 80% of those with obesity.[2] It is a slow-progressing condition in which fat builds up in the liver, causing inflammation and scarring, and can lead to cirrhosis (severe liver scarring), liver cancer, liver failure, liver transplantation and death.

Symptoms of MASH include fatigue, muscle weakness and unexplained weight loss, but the condition is often not diagnosed until it becomes severe. Individuals with type 2 diabetes, obesity, high cholesterol and/or high blood pressure are particularly vulnerable to MASH.[3]

In 2024 the FDA granted accelerated approval to resmetirom (REZDIFFRA), an oral medication for MASH in adults with moderate to advanced liver fibrosis.[4] Public Citizen’s Health Research Group designated resmetirom as a Do Not Use drug because of concerns about its clinical benefits and its long-term safety and effectiveness.[5]

Semaglutide

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that mimics a natural hormone, glucagon, that stimulates insulin release and appetite.[6] Common adverse effects include nausea, diarrhea, abdominal pain, headache, dyspepsia (indigestion), dizziness, hypoglycemia in patients with type 2 diabetes, and gastroenteritis.[7]

Semaglutide was initially approved in 2017 under the brand name OZEMPIC as an adjunct to diet and exercise for glycemic control in adults with type 2 diabetes. It was later approved under this brand name for cardiovascular and kidney indications for adults with type 2 diabetes.[8]

Subsequently, semaglutide has been approved under the brand name Wegovy for additional indications. One indication is chronic weight management in adults and pediatric patients aged 12 years and older with obesity and adults with overweight and at least one weight-related comorbid condition.[9] A second indication is to reduce the risk of major adverse cardiovascular events (death and nonfatal heart attacks and strokes) in adults with cardiovascular disease and either obesity or overweight. MASH treatment is now the third indication. The MASH indication does not include patients with cirrhosis.[10]

As Wegovy, semaglutide is administered as single-dose prefilled pens that deliver preset doses (0.25 milligrams [mg], 0.5 mg, 1 mg, 1.7 mg or 2.4 mg) once weekly via subcutaneous injection. For patients with MASH, the typical maintenance dosage is 2.4 mg once weekly, which can be reduced to 1.7 mg for those who do not tolerate the higher dose.

Semaglutide has a boxed warning that notes an increased risk of a type of thyroid tumor. It is also contraindicated in patients with certain thyroid cancers and an endocrine cancer syndrome.

The ongoing clinical trial supporting approval[11]

The FDA’s approval of semaglutide for MASH was based on the interim results of an ongoing phase 3, randomized, double-blind, placebo-controlled trial, which were published in 2025. The trial randomly assigned eligible adults with liver-biopsy-defined MASH to either weekly semaglutide (534 participants) or placebo (266 participants) injections; both groups received lifestyle interventions to promote caloric-intake reductions and exercise.

At a planned interim analysis after 72 weeks, the primary endpoint of MASH resolution without worsening of liver fibrosis was met in 62.9% of participants in the treatment group and 34.2% of participants in the placebo group. In addition, 36.8% of participants in the treatment group showed a reduction in liver scarring with no worsening of MASH, compared with 22.4% of those in the placebo group.

The phase 3 trial of semaglutide is ongoing and will continue for 240 weeks. The goal is to determine whether the improvements seen after 72 weeks lead to decreases in liver-related clinical events (for example, cirrhosis, liver failure and death) after 240 weeks.[12] The drug label notes that the continued approval of semaglutide for MASH “may be contingent upon the verification and description of the clinical benefit in a confirmatory trial.” The FDA is also requiring the manufacturer to modify the ongoing clinical trial to formally evaluate the pancreatic safety of semaglutide and bone-related adverse events.[13]

What You Can Do

If you have MASH with moderate to advanced liver fibrosis, talk to your clinician about semaglutide and other treatment approaches. The cornerstones of therapy are avoidance of alcohol; diet and exercise to support sustained and healthy weight loss; and management of other conditions, such as diabetes, hyperlipidemia and high blood pressure. In many people, MASH stabilizes or improves; even in advanced forms, the disease may take years to progress.

Be aware that semaglutide has adverse effects and many warnings and precautions, such as for hypoglycemia, acute pancreatitis, and severe gastrointestinal adverse reactions and illnesses.

The long-term safety of semaglutide for MASH has yet to be determined, and the effectiveness for liver-related clinical endpoints, such as cirrhosis, liver failure and death, has not been established. For these reasons, Public Citizen’s Health Research Group has designated semaglutide for MASH as Do Not Use for Seven Years.
 

References

[1] Food and Drug Administration. FDA approves treatment for serious liver disease known as ‘MASH’. August 15, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash. Accessed December 10, 2025.

[2] Tilg H, Petta S, Stefan N, Targher G, et al. Metabolic dysfunction–associated steatotic liver disease in adults: A review. JAMA. November 10, 2025. doi: 10.1001/jama.2025.19615. Accessed December 10, 2025.

[3] Metabolic Dysfunction-Associated Steatohepatitis? Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/22988-nonalcoholic-steatohepatitis. Accessed December 10, 2025.

[4] Food and Drug Administration. FDA approves first treatment for patients with liver scarring due to fatty liver disease. March 14, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash. Accessed December 10, 2025.

[5] Resmetirom (REZDIFFRA) for nonalcoholic steatohepatitis (fatty liver disease): Do not use. Worst Pills Best Pills News. September 2024. https://www.worstpills.org/newsletters/view/1620. Accessed December 10, 2025.

[6] Semaglutide (WEGOVY) for weight loss: Substantial risks, including weight regain. Worst Pills Best Pills News. August 2023. https://www.worstpills.org/newsletters/view/1545#ref_8. Accessed December 10, 2025.

[7] Food and Drug Administration. FDA approves treatment for serious liver disease known as ‘MASH’. August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215256s023lbl.pdf. Accessed December 10, 2025.

[8] Novo Nordisk. Label: semaglutide (Ozempic). January 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209637s035,209637s037lbl.pdf. Accessed December 10, 2025

[9] Novo Nordisk. Label: semaglutide (Wegovy). August 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215256s024lbl.pdf. Accessed December 10, 2025.

[10] Ibid.

[11] Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. NEJM. April 30, 2025. https://www.nejm.org/doi/abs/10.1056/NEJMoa2413258. Accessed December 10, 2025.

[12] Food and Drug Administration. FDA approves treatment for serious liver disease known as ‘MASH’. August 15, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash. Accessed December 10, 2025.

[13] Food and Drug Administration. Letter of accelerated approval of semaglutide (Wegovy) for MASH. August 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215256Orig1s024ltr.pdf Accessed December 10, 2025.