FDA Approves Semaglutide Injection for Noncirrhotic MASH Patients

The US Food and Drug Administration (FDA) has granted approval for Novo Nordisk’s semaglutide injection, branded as Wegovy, at a dosage of 2.4 mg for adults diagnosed with metabolic dysfunction-associated steatohepatitis (MASH) accompanied by moderate to advanced fibrosis, excluding those with cirrhosis. This decision, announced on August 15, 2025, is intended to be used alongside a reduced-calorie diet and increased physical activity.

The approval is anchored in the findings from the phase 3 ESSENCE trial, which assessed the impact of the once-weekly semaglutide injection on liver health over 72 weeks. “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,” stated Arun Sanyal, MD, the Director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University. He emphasized the potential severity of untreated MASH, which can lead to life-threatening complications.

Semaglutide was initially approved in 2021 to aid adults with obesity or those with excess weight and related medical issues in losing weight and maintaining that loss. Its use was expanded in 2022 to include children aged 12 years and older facing obesity. In 2024, the medication was recognized for reducing the risk of major cardiovascular incidents, including death, heart attacks, or strokes in adults with known heart disease, obesity, or overweight.

The ESSENCE trial, comprising two parts, investigated the efficacy of the 2.4 mg semaglutide injection in adults with MASH and moderate to advanced liver fibrosis. A total of 1,197 participants were randomly assigned to receive either semaglutide or a placebo, along with standard care for a duration of 240 weeks. The first part aimed to evaluate the treatment’s impact on liver histology at 72 weeks, utilizing biopsy samples from the initial 800 randomized patients.

The trial yielded significant results. The first primary endpoint revealed that 63% of participants receiving semaglutide achieved resolution of steatohepatitis without worsening liver fibrosis, compared to 34% in the placebo group, marking a statistically significant difference of 29 (95% CI, 21-36). Additionally, 37% of those treated with semaglutide showed improvement in liver fibrosis and no worsening of steatohepatitis, versus 22% in the placebo group, a difference of 14 (95% CI, 8-21).

Furthermore, a secondary endpoint at Week 72 indicated that 33% of the semaglutide group experienced both resolution of steatohepatitis and improvement in liver fibrosis, compared to 16% in the placebo group, demonstrating a statistically significant difference of 17 (95% CI, 10-23). Notably, 83.5% of patients receiving semaglutide maintained the target dose of 2.4 mg until Week 72.

Dave Moore, Executive Vice President of US Operations at Novo Nordisk, remarked, “For far too long, this disease has remained unrecognized, undiagnosed, and often untreated, despite impacting so many people. 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.”

The FDA’s approval of semaglutide for MASH treatment represents a significant advancement in addressing this previously overlooked condition, aligning with the growing body of evidence supporting the clinical benefits of semaglutide for various chronic health issues.