FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH

The US Food and Drug Administration (FDA) has approved Novo Nordisk’s semaglutide (Wegovy) injection 2.4 mg for the treatment adults with metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced fibrosis, but not with cirrhosis, in conjunction with a reduced calorie diet and increased physical activity.1

According to an August 15, 2025, release from Novo Nordisk, the decision is based on results from the phase 3 ESSENCE trial investigating the effects of once-weekly semaglutide 2.4 mg injection on liver histology in adults with MASH and moderate to advanced liver fibrosis at week 72.1

"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 statement.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."

Hear from Sanyal about the ESSENCE data in this episode of Diabetes Dialogue!

Initially approved in 2021 with a reduced calorie meal plan and increased physical activity to help adults with obesity, or some adults with excess weight (overweight) who also have weight-related medical problems to lose weight and keep the weight off, semaglutide’s indication was expanded in 2022 to include children ≥ 12 years of age with obesity. In 2024, semaglutide was approved to reduce the risk of major cardiovascular events such as death, heart attack, or stroke in adults with known heart disease and either obesity or overweight.1

Semaglutide’s use in MASH was explored in the ESSENCE trial, a 2-part phase 3 trial evaluating the effect of once-weekly subcutaneous semaglutide 2.4 mg in adults with MASH and moderate to advanced fibrosis. A total of 1197 participants were randomly assigned in a 2:1 to receive semaglutide 2.4 mg or placebo, on top of standard of care for 240 weeks.1,2

In part 1, the objective was to demonstrate the beneficial impact of treatment with semaglutide 2.4 mg on liver histology at 72 weeks based on biopsy sampling from the first 800 randomized patients. In part 2, which is ongoing, the objective is to demonstrate treatment with semaglutide 2.4 mg reduces the risk of liver-related clinical events compared to placebo at 240 weeks.1,2

In ESSENCE, the first primary endpoint showed 63% of people treated with semaglutide 2.4 mg injection (n = 534) achieved resolution of steatohepatitis and no worsening of liver fibrosis compared to 34% on placebo (n = 266) with a statistically significant difference in response rate versus placebo of 29 (95% CI, 21-36). Additionally, the second primary endpoint showed 37% of people treated with semaglutide 2.4 mg achieved improvement in liver fibrosis and no worsening of steatohepatitis compared to 22% on placebo with a statistically significant difference in response rate versus placebo of 14 (95% CI, 8-21).1

Additionally, a confirmatory secondary endpoint at Week 72 showed 33% of patients treated with semaglutide 2.4 mg achieved both resolution of steatohepatitis and improvement in liver fibrosis compared to 16% on placebo with a statistically significant difference in response rate versus placebo of 17 (95% CI, 10-23). A total of 83.5% of the patients in the semaglutide group maintained the target dose of 2.4 mg until Week 72.1

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

References

1. Novo Nordisk. Wegovy® approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. August 15, 2025. Accessed August 15, 2025. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=916417

2. Brooks A. ESSENCE: Semaglutide Improves Fibrosis, Resolves Steatohepatitis in MASH. November 1, 2024. Accessed August 15, 2025. https://www.hcplive.com/view/essence-semaglutide-improves-fibrosis-resolves-steatohepatitis-in-mash