FDA grants accelerated approval of Wegovy for MASH

The US Food and Drug Administration approved Wegovy (semaglutide) injection 2.4 mg on August 15, 2025, to treat adults with metabolic dysfunction-associated steatohepatitis (MASH) who have moderate to advanced liver scarring (fibrosis) but not cirrhosis, alongside a reduced-calorie diet and increased physical activity ^[2]. It is the first GLP-1 receptor agonist approved for this condition ^[2][4].

MASH, formerly called nonalcoholic steatohepatitis or NASH, is a severe form of fatty liver disease in which fat buildup in the liver triggers inflammation and scarring ^[1]. The FDA estimates about 6% of US adults — roughly 14.9 million people — have MASH, and that the number is growing ^[1]. Novo Nordisk describes it as affecting about 1 in 20 people in the US, and says roughly 1 in 3 people worldwide with overweight or obesity also have MASH ^[2]. Many people have no symptoms until serious liver damage has occurred; untreated, the disease can progress to cirrhosis, liver cancer, liver transplant, or death ^[1][2].

What the trial showed

Approval came through the accelerated approval pathway, which lets drugs for serious conditions reach the market based on a surrogate measure — here, liver biopsy findings — with more data required afterward to confirm a benefit in how patients feel, function, or survive ^[1].

The evidence comes from Part 1 of the ongoing phase 3 ESSENCE trial, which enrolled 1,197 adults with MASH and stage F2 to F3 fibrosis, randomly assigned 2:1 to semaglutide 2.4 mg weekly or placebo on top of standard care ^[2][3]. A planned interim analysis at week 72 covered 800 participants: 534 on Wegovy and 266 on placebo, all of whom also received lifestyle counseling; participants were on stable doses of lipid-lowering, glucose-management and weight-loss medicines ^[1].

At week 72, 63% of the Wegovy group had resolution of steatohepatitis with no worsening of fibrosis, versus 34% on placebo — a 29 percentage-point difference (95% CI, 21-36) ^[1][2]. For the second endpoint, 37% on Wegovy had improved fibrosis with no worsening of steatohepatitis, versus 22% on placebo, a 14-point difference (95% CI, 8-21) ^[1][2]. A secondary endpoint found 33% achieved both outcomes versus 16% on placebo ^[2][4]. Sources differ slightly on how many people stayed at the target dose: Novo Nordisk reported 83.5% through week 72 ^[2], Healio reported nearly 84% ^[3], and AJMC reported about 88% ^[4].

On safety, the FDA lists common side effects including nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, indigestion, dizziness, bloating, burping, low blood sugar in people with type 2 diabetes, gas, stomach flu, reflux and colds ^[1]. People with a personal or family history of medullary thyroid cancer, with multiple endocrine neoplasia type 2, or with known sensitivity to semaglutide or Wegovy ingredients should not take the drug ^[1]. AJMC reported serious adverse events were mainly gastrointestinal, occurring in 13.4% of the cohort, and led 2.6% of the semaglutide group and 3.3% of the placebo group to leave the trial early; nine participants died during the trial, three on semaglutide and six on placebo, with no evident clustering of cause ^[4].

Why it matters for patients

This is a new, narrowly defined indication, not a broadening of Wegovy's weight-loss label. It applies to adults with biopsy-confirmed MASH and stage 2 or 3 fibrosis, and specifically excludes cirrhosis ^[2]. Hepatologist Rohit Loomba said semaglutide and resmetirom (Rezdiffra) "are not approved for treatment of MASH cirrhosis, and hence, these agents should only be used among those with MASH with stage 2 or 3 disease" ^[3]. Semaglutide joins resmetirom, an oral thyroid hormone receptor-beta agonist approved in 2024, as the only approved drugs for MASH with fibrosis ^[4].

Because this is accelerated approval, the liver benefit is measured by biopsy changes, not yet by fewer transplants or deaths ^[1]. Novo Nordisk's own label language notes an ongoing study is required to confirm clinical benefit ^[2].

Whether insurers will cover Wegovy specifically for MASH, what prior-authorization rules will apply, or what the cost will be for this indication is not addressed in any of the sources reviewed here, so it is not yet known. Diagnosis is also a practical hurdle: the trial used liver biopsy to stage fibrosis ^[1], and MASH often goes undiagnosed because early symptoms are vague or absent ^[2].

What happens next

ESSENCE continues to 240 weeks to test whether semaglutide lowers the risk of liver-related clinical events compared with placebo ^[2][3]. Results from Part 2 are expected in 2029 ^[4]. Novo Nordisk filed for approval in the European Union in February 2025 and in Japan in May 2025 ^[2].