Semaglutide Receives FDA Approval for Treatment of MASH

The FDA has approved a 2.4 mg injection of semaglutide (Wegovy; Novo Nordisk) for the treatment of adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis, marking the treatment as the first and only glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved for this patient population.¹

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"Today's decision by the FDA reflects the continued progress in how we understand and treat patients with MASH, bringing us closer to care that meets the needs of people living with this disease," Arun Sanyal, MD, director, Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, said in a news release.¹

MASH & Obesity

Nearly 1 in 20 US individuals are living with MASH—a severe form of fatty liver disease that can cause life-threatening outcomes if not treated properly—and around 1 in 3 individuals who are living with overweight or obesity also have MASH. This is caused by excess fat building up in the liver, leading to inflammation and scarring of the liver over time. Individuals with MASH usually are asymptomatic in the early stages or present symptoms that are not closely related to the disease, leading to delayed diagnoses and treatment.¹

"For far too long, this disease has remained unrecognized, undiagnosed, and often untreated, despite impacting so many people," Dave Moore, executive vice president of US Operations at Novo Nordisk, said in the news release.¹

ESSENCE Clinical Trial

This approval is supported by results from the phase 3 ESSENCE trial (NCT04822181) that evaluated the effect of once-weekly subcutaneous semaglutide 2.4 mg in adults with non-cirrhotic MASH and stage 2 or 3 liver fibrosis. The 2-part trial included a total of 1197 individuals that were randomly assigned 2 to 1 to receive 2.4 mg of semaglutide or placebo, along with standard of care for 240 weeks. The first part of the study aimed to demonstrate that treatment with semaglutide improves liver histology compared with a placebo in patients with MASH and moderate to severe fibrosis. The second part, which is ongoing, is designed to demonstrate that semaglutide treatment lowers the risk of liver-related clinical events over 240 weeks.^1,2

Treatment with semaglutide was more effective than a placebo. The first primary end point showed that 63% of patients treated with semaglutide achieved resolution of MASH with no worsening of liver fibrosis, compared with 34% of patients on the placebo. The second primary end point found that 37% of individuals on semaglutide achieved an improvement in liver fibrosis with no worsening of MASH, versus 22% on the placebo.¹

Additionally, at week 72, 33% of patients treated with semaglutide achieved both resolution of MASH and improvement in liver fibrosis, compared with 16% on the placebo. The study authors also noted that 83.5% of patients in the semaglutide group were able to maintain the target dose of 2.4 mg throughout the 72-week period.¹

"If left untreated, MASH can lead to serious and potentially fatal outcomes. The clinical evidence seen in ESSENCE underscores the promise of this approach to treating adults with MASH with moderate to advanced liver fibrosis,” Sanyal said in the news release.¹

Semaglutide Indications

Semaglutide received initial approval in 2017, followed by a second approval in 2021 for the treatment of individuals with obesity and overweight in addition to a reduced-calorie meal plan and exercise, which was expanded to children aged 12 years and older with obesity in 2022. In 2024, the injection was approved to reduce the risk of major cardiovascular events in individuals with obesity or overweight, aimed to prevent death, heart attack, or stroke.^3-5

"The FDA's conditional approval of [semaglutide] for the treatment of adults with noncirrhotic MASH marks a truly pivotal milestone and a significant step forward for the MASH community and those seeking new options," Moore concluded. "This builds on the expanding body of evidence demonstrating the clinical benefits of semaglutide across a range of chronic conditions, including diabetes, obesity, cardiovascular disease, and chronic kidney disease.”¹

REFERENCES

1. Wegovy® approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. Novo Nordisk. News release. August 15, 2025. Accessed August 18, 2025. 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

2. Research study on whether semaglutide works in people with non-alcoholic steatohepatitis (NASH) (ESSENCE). Updated July 20, 2025. Accessed August 18, 2025. https://clinicaltrials.gov/study/NCT04822181

3. FDA Approves Treatment for Serious Liver Disease Known as ‘MASH’. FDA. News release. August 15, 2025. Accessed August 18, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash?utm_medium=email&utm_source=govdelivery

4. Coppock K. FDA Approves Prescription Weight Loss Therapy for Adults With Obesity. Pharmacy Times. June 4, 2021. Accessed August 18, 2025. https://www.pharmacytimes.com/view/fda-approves-prescription-weight-loss-therapy-for-adults-with-obesity

5. Gallagher A. FDA Approves Semaglutide for New Indication Involving Cardiovascular Disease. Pharmacy Times. March 8, 2025. Accessed August 18, 2025. https://www.pharmacytimes.com/view/fda-approves-semaglutide-for-new-indication-involving-cardiovascular-disease