FDA Approves Semaglutide to Treat MASH With Moderate to Advanced Fibrosis

The FDA approved semaglutide (Wegovy) as the first and only glucagon-like peptide-1 (GLP-1) receptor agonist to treat metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced fibrosis but not cirrhosis of the liver. The 2.4 mg injection should be used in conjunction with a reduced-calorie diet and increased physical activity.¹

FDA approves Wegovy for treating metabolic dysfunction-associated steatohepatitis, marking a breakthrough in liver health management and patient care. | Image Credit: B-design - stock.adobe.com

"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 of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, said in a news release.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."

The approval was based on the phase 3 ESSENCE (NCT04822181) trial, which evaluated the effects of a once weekly Wegovy 2.4 mg injection on liver histology at week 72. The trial was a 2-part, randomized, multicenter, double-blind study that followed patients with MASH and stage 3 or 4 fibrosis. Part 1 was conducted at 253 sites in 37 counties and included a 14-week screening period. Following the screening period, the treatment period was 240 weeks, with 0 to 72 weeks making up part 1 and 0 to 240 making up part 2, and then a 7-week follow-up period followed.

In the first part, there were 800 patients who received treatment between May 27, 2021, and April 18, 2024, and 1200 individuals were included in part 2. Patients received once weekly subcutaneous semaglutide 2.4 mg or the placebo in a 2:1 ratio, which was added to the standard of care.²

The primary end points in part 1 included resolution of steatohepatitis with no worsening fibrosis and improvement of liver fibrosis with no worsening steatohepatitis. Confirmatory secondary end points included change in body weight, resolution of steatohepatitis and improvement in liver fibrosis, and change in Short Form 36 Bodily Pain. As for part 2, the primary outcome included cirrhosis-free survival at week 240.²

Investigators reported that the resolution of steatohepatitis without worsening fibrosis was seen in 62.9% of patients in the semaglutide group and in 34.3% of patients in the placebo group. Further, a reduction in liver fibrosis without worsening steatohepatitis was reported in 36.8% of patients and 22.4% of patients, respectively.

For secondary outcomes, investigators found the combined resolution of steatohepatitis and reduction in liver fibrosis was 32.7% and 16.1%, respectively. The mean change in body weight was –10.5% and –2.0%, respectively. There were no significant differences in mean changes in body pain between the 2 groups, and gastrointestinal adverse events were more common in patients receiving semaglutide.³

"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 "The FDA's conditional approval of Wegovy 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."

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REFERENCES

1. Wegovy approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. News release. Novo Nordisk. 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. Newsome PN, Sanyal AJ, Engebretsen KA, et al. Semaglutide 2.4 mg in Participants With Metabolic Dysfunction-Associated Steatohepatitis: Baseline Characteristics and Design of the Phase 3 ESSENCE Trial. Aliment Pharmacol Ther. 2024;60(11-12):1525-1533. doi:10.1111/apt.18331

3. Mantovani A, Morandin R, Fiorio V, et al. Glucagon-Like Peptide-1 Receptor Agonists Improve MASH and Liver Fibrosis: A Meta-Analysis of Randomised Controlled Trials. Liver Int. 2025;45(9):e70256. doi:10.1111/liv.70256