FDA Approves Semaglutide for MASH With Fibrosis

The FDA has granted accelerated approval to semaglutide (Wegovy; Novo Nordisk) injection 2.4 mg for the treatment of adults with metabolic dysfunction–associated steatohepatitis (MASH) with moderate to advanced liver fibrosis, making it the first glucagon-like peptide-1 (GLP-1) receptor agonist approved for this indication.¹

A Novo Nordisk new release noted that semaglutide is not currently indicated for patients with cirrhosis, and it must be complemented with a reduced-calorie diet and increased physical activity. Semaglutide now joins resmetirom (Rezdiffra; Madrigal Pharmaceuticals)—a once-daily, oral, thyroid hormone receptor-β selective agonist—as the only approved treatments for patients with MASH and liver fibrosis.²

Approval Based on ESSENCE Results

The approval was based on part 1 of the phase 3 ESSENCE trial (NCT04822181), which evaluated semaglutide in adults with MASH and stage F2 to F3 liver fibrosis.³ Investigators found significant improvements in liver outcomes with once-weekly semaglutide 2.4 mg compared with placebo.

At 72 weeks, about 63% of participants treated with semaglutide achieved resolution of steatohepatitis without worsening fibrosis, compared with 34% in the placebo arm, marking a 29–percentage point difference (95% CI, 21-36). Additionally, 37% of patients on semaglutide achieved improvement in fibrosis without worsening steatohepatitis compared with 22% on placebo, with a difference of 14 percentage points (95% CI, 8-21).

A third of participants in the treatment arm achieved both resolution of steatohepatitis and improvement in fibrosis (33%) vs 16% in the placebo arm, with a difference of 17 percentage points (95% CI, 10-23). About 88% of patients in the semaglutide group maintained the target 2.4-mg dose through week 72.

"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,” Dave Moore, MBA, executive vice president of US operations at Novo Nordisk, said in a news release.⁴ “This builds on the expanding body of evidence demonstrating the clinical benefits of semaglutide across a range of chronic conditions including diabetes, obesity, cardiovascular and chronic kidney disease."

Addressing an Unmet Need in Liver Disease

Semaglutide joins resmetirom as the only approved treatments for MASH with fibrosis. | Image credit: wladimir1804 – stock.adobe.com

MASH, formerly known as nonalcoholic steatohepatitis (NASH), is a progressive form of fatty liver disease characterized by inflammation and scarring, affecting approximately 1 in 20 people in the US.⁵ Patients are often asymptomatic until the disease has advanced, which contributes to underdiagnosis and delayed treatment.⁴

Left unmanaged, MASH can progress to cirrhosis, liver cancer, and liver failure requiring transplantation. The condition is closely tied to obesity and metabolic dysfunction, with estimates suggesting that 1 in 3 people worldwide who have overweight or obesity also have MASH.

Expanding the Role of Semaglutide

Under the brand name Wegovy, semaglutide has made its name in obesity care since its initial FDA approval in 2021, with subsequent label expansions including adolescents with obesity in 2022 and for the reduction of major adverse cardiovascular events (MACE) in adults with established cardiovascular disease and obesity or overweight in 2024.³

The newest indication extends its therapeutic reach into hepatology, supported by a growing body of evidence linking weight loss and GLP-1 receptor agonist therapy to improvements in liver health.¹

Regarding safety, serious adverse events were mainly gastrointestinal—common with semaglutide—occurring in 13.4% of the cohort; this caused 2.6% of the semaglutide group and 3.3% of the placebo group to end the trial early.³ Nine patients died during the trial, including 3 patients in the semaglutide group and 6 in the placebo group, though there was no evident clustering of cause of death, according to the researchers.

The second part of the ESSENCE trial will extend to 240 weeks, focusing on whether semaglutide lowers the risk of liver-related clinical events compared with placebo.¹ Findings are expected to read out in 2029, according to the release.

References

1. Novo Nordisk A/S: Wegovy® approved in the US for the treatment of MASH. News release. Novo Nordisk. August 15, 2025. Accessed August 18, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916416
2. Joszt L. FDA approves resmetirom, first treatment for NASH with liver fibrosis. AJMC^®. March 14, 2024. Accessed August 18, 2025. https://www.ajmc.com/view/fda-approves-resmetirom-first-treatment-for-nash-with-liver-fibrosis
3. Klein HE. Semaglutide may reduce liver fibrosis in patients with MASH. AJMC. May 12, 2025. Accessed August 18, 2025. https://www.ajmc.com/view/semaglutide-may-reduce-liver-fibrosis-in-patients-with-mash
4. Wegovy® approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. News release. PR Newswire. 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
5. Younossi ZM, Mangla KK, Chandramouli AS, Lazarus JV. Estimating the economic impact of comorbidities in patients with MASH and defining high-cost burden in patients with noncirrhotic MASH. Hepatol Commun. 2024;8(8):e0488. doi:10.1097/HC9.0000000000000488