With a new endorsement from the FDA, Novo Nordisk’s Wegovy has picked up its third indication and become the second drug approved in a severe form of fatty liver disease.
Shortly after market close Friday, the FDA signed off on an accelerated approval for Wegovy 2.4 mg to treat adult metabolic dysfunction-associated steatohepatitis (MASH) patients with moderate to advanced fibrosis, or liver scarring, who don’t have cirrhosis of the liver. The approval covers Wegovy in combination with a reduced calorie diet and increased physical activity, according to an Aug. 15 press release from Novo.
The conditional nod was granted based on improvement of MASH and liver scarring in patients who received Wegovy in the first tranche of a two-part clinical trial, Novo explained. The second part of that program, dubbed Essence, is ongoing and expected to read out around 2029, Novo has previously communicated.
MASH, which formerly went by the name nonalcoholic steatohepatitis (NASH), occurs when a person has excess fat cells in their liver that cause chronic inflammation, potentially leading to liver damage.
By Novo’s estimate, the disease affects 1 in 20 people in the U.S. and occurs in roughly 1 in 3 people globally who are overweight or obese. The condition can be tricky to diagnose early on but, if left untreated, MASH can progress to cause serious health problems such as cirrhosis, liver cancer and the need for a liver transplant, Novo explained.
In the Essence study, which looked at once-weekly Wegovy in MASH patients whose liver fibrosis had advanced to stage F2 or F3, 63% of patients on Novo’s GLP-1 achieved resolution of steatohepatitis with no worsening of their fibrosis at 72 weeks. That compared to just 34% of patients who received placebo.
On the study’s second primary endpoint, Wegovy helped 37% of patients achieve improvement in liver fibrosis with no worsening of their steatohepatitis, versus 22% in the study’s control arm.
When looking at a separate, confirmatory secondary endpoint, Wegovy helped 33% of patients achieve both resolution of steatohepatitis and improvement in liver fibrosis by Week 72, compared to a rate of just 16% in the placebo cohort, Novo explained.
Many drugmakers have tried their hand at developing MASH treatments, and many of those efforts have resulted in high-profile stumbles. Novo is no exception, having delivered disappointing study results on semaglutide—the molecule behind Wegovy—in the disease back in 2022. Friday’s nod vindicates Novo’s decision to continue pursuing development of the drug in MASH.
Wegovy is also approved in obesity and for cardiovascular risk reduction, while its sister medicine Ozempic is cleared in Type 2 diabetes. Ozempic and Wegovy kicked off a GLP-1 weight loss craze around the globe, though Novo has gradually lost its sales edge to Eli Lilly in the crucial U.S. obesity market.
Elsewhere, Madrigal Pharmaceuticals made history last March when the FDA approved its medicine Rezdiffra (resmetirom) as the first MASH drug in the U.S. Madrigal and Novo’s drugs are approved in similar MASH patient populations, though Rezdiffra and Wegovy have fundamentally different mechanisms of action given that Rezdiffra is a thyroid receptor-beta agonist, which targets the liver directly.
GLP-1s like Wegovy, on the other hand, work by mimicking the glucagon-like peptide-1 hormone and are thought to help improve the disease through their anti-inflammatory effects and by reducing fat levels in the liver.
There is clearly pent-up demand for MASH treatments given Rezdiffra’s sales trajectory so far. As of 2025’s first quarter, Rezdiffra had beat Wall Street’s sales expectations four quarters in a row. That upward momentum carried through into the second quarter, as well, when Madrigal reported Rezdiffra sales of $212.8 million.
Though Wegovy has come in second across the FDA’s MASH finish line, Novo still has the potential to carve out a lucrative chunk of the market for the severe liver disease.
Despite Madrigal’s first-mover advantage in MASH, “this is a large market with room for many players and treatment options,” analysts at Evercore ISI wrote last year following Novo’s Nov. 1 data drop for semaglutide in the disease.
Outside the U.S., Novo has also filed for Wegovy MASH approvals in the EU and Japan.
Multiple other drugmakers are aiming their development engines at the disease, too, with Novo’s chief rival Lilly unveiling detailed positive data on its dual GIP/GLP-1 med tirzepatide in the condition last June.
In the midstage Synergy-NASH trial, 54.9% of patients on 5 mg tirzepatide, 51.3% of patients on 10 mg tirzepatide and 51% of patients on 15 mg tirzepatide saw their fibrosis decrease by at least one stage without their MASH worsening. At the time, Evercore ISI analysts called the data “solid” and said the results “may be slightly better” than those for Madrigal’s Rezdiffra.