On 15 August 2025, Novo Nordisk announced that the US Food and Drug Administration (FDA) approved a new indication for Wegovy 2.4 mg (semaglutide) injection. This makes it the only glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved by the FDA to help treat adults with Metabolic Dysfunction -Associated Steatohepatitis (MASH) who have moderate to advanced liver scarring (fibrosis), but not cirrhosis. The treatment is intended to be used alongside a reduced-calorie diet and increased physical activity.
About the Disease: MASH
MASH is recognized as the most common chronic liver disease, affecting 30% of adults worldwide and previously called Nonalcoholic Steatohepatitis (NASH). It is characterised by the accumulation of excess fats (steatosis), along with inflammation (hepatitis), injury, and scarring (fibrosis) in the liver. MASH is often linked to obesity, Type 2 diabetes and other metabolic disorders. If not treated, it may progress to cirrhosis or liver cancer.
Common Symptoms of MASH
MASH often develops quietly, without early signs, until it leads to significant liver damage. It tends to progress slowly over many years. When symptoms do show up, they might include:
- Fatigue
- Discomfort or pain in the upper right side of the abdomen
- Unexplained weight loss
- Muscle weakness or muscle loss
- Yellowing of the eyes and skin in the advanced stage
The Trial Behind the Approval: ESSENCE
The FDA’s accelerated approval of Wegovy was backed by data from the ongoing Phase 3 ESSENCE trial.
Key Findings (Week 72 Results):
- 63% of people taking Wegovy achieved MASH resolution without worsening fibrosis, compared to 34% on the placebo.
- 37% of Wegovy participants showed improvement in liver fibrosis without worsening MASH, versus 22% with placebo.
- A notable 83.5% of individuals in the semaglutide group maintained the target dose of 2.4 mg through Week 72.
The ESSENCE trial will continue for a total of 240 weeks, allowing researchers to confirm whether the improvements in inflammation and fibrosis translate into long-term benefits in liver health and survival.
Takeaway
The FDA’s conditional approval of Wegovy for adults with noncirrhotic MASH marks a significant milestone in liver disease treatment, providing hope to patients with MASH seeking additional options.
Further Reading
- https://www.prnewswire.com/news-releases/wegovy-approved-by-fda-for-the-treatment-of-adults-with-noncirrhotic-mash-with-moderate-to-advanced-liver-fibrosis-302531394.html.
- https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash
- Harrison SA, Dubourg J. Liver biopsy evaluation in MASH drug development: Think thrice, act wise. J Hepatol. 2024 Nov;81(5):886-894.https://pubmed.ncbi.nlm.nih.gov/38879176/
- Ghazanfar H, Javed N, Qasim A, Zacharia GS, Ghazanfar A, Jyala A, Shehi E, Patel H. Metabolic Dysfunction-Associated Steatohepatitis and Progression to Hepatocellular Carcinoma: A Literature Review. Cancers (Basel). 2024 Mar 20;16(6):1214. https://pmc.ncbi.nlm.nih.gov/articles/PMC10969013/#sec1-cancers-16-01214
- https://my.clevelandclinic.org/health/diseases/22988-nonalcoholic-steatohepatitis
