Targeting GLP-1 receptors now have the blessing of the FDA, is a way to treat fatty liver disease with Novo Nordisk’s weekly injectable drug Wegovy, becoming the second approved treatment for this prevalent metabolic disease.
In MASH, the abbreviation for steatohepatitis associated with metabolic dysfunction, the accumulation of fat in the liver can cause inflammation and scars in the organs, which is called fibrosis. According to the FDA, an estimated 14.9 million adults in the United States have mashed potatoes, and the prevalence is growing. Later on Friday, Wegovy's regulatory decision covered treatment for adults whose mashed potatoes resulted in moderate to severe fibrosis. These patients must not develop it into cirrhosis, which is the most advanced stage of the disease. Just like the previous approvals for obesity, Wegovy’s Mash approval covers the use of the drug in diet and exercise.
The active ingredient in Wegovy is Semaglutide, a peptide designed to target and activate GLP-1 receptors. This method can promote fullness and delay stomach emptying, helping patients feel full and making them eat less. This mechanism of action supports the initial approval of the drug in obesity. Wegovy works for treating Mash but reducing body fat is thought to lead to liver benefits. The approval of Wegovy at the 2.4 mg dose in MASH is based on temporary results from a placebo-controlled Phase 3 clinical trial that evaluated 1,197 patients with moderate to severe Mash. At week 72, 800 trial participants showed that 63% achieved MASH resolution and had no worsening fibrosis, a goal of 34% in the placebo group.
Wegovy's regulatory decision in MASH is based on a 72-week interim result to accelerate approval. This earnings must be confirmed by ongoing phase 3 trials. The researchers will examine whether the inflammation and scar improvements observed during the 72-week period translate into death, liver transplants and other liver-related events measured at 240 weeks.
Wegovy is approved to treat obesity in 2021. Last year, the drug expanded recognition in the United States and Europe, including reducing the risk of cardiovascular disease, heart attacks and stroke in adults with obesity or overweight. Among all approved uses by Wegovy, Novo Nordisk reported sales of more than 36.8 billion Danish Krone (approximately $5.7 billion) in the first half of this year.
“The FDA's conditional approval of Wegovy for treatment with nondiagnostic Mash for adults is a truly critical milestone, and it is an important step for the MASH community and those seeking new options,” said Dave Moore, executive vice president of U.S. executive vice president of Novo Nordisk, in a prepared statement.
With its latest FDA approval, Wegovy will now compete with Madrigal Pharmaceuticals drug Rezdiffra, whose accelerated approval last year made it the first Mash Drug. Made in the form of daily pills, the small molecule mediates metabolic activity in the organs by targeting and activating a receptor called thyroid hormone receptor beta (Thr-beta). In a report on second-quarter 2025 financial results, the company said Rezdiffra had revenues of more than $350 million in the first half of the year.
Thomas Smith, an analyst at Leerink Partners, said in a note sent to investors on Saturday that his company believes drugs like Wegovy will find some aspects of using MASH, the company expects drug combinations across multiple drug categories to become the standard of care for the disease. Based on discussions with clinicians, Leerink expects enterohemagglutinin mimetics, including Wegovy, to be new MASH patients with metabolic features of the disease, such as obesity and cardiovascular disease, and that these comorbidities are not currently treated with medication.
Leerink is still projecting a strong market absorption for Rezdiffra, and Madrigal drugs are the first choice for patients who have taken GLP-1 agonists. The company notes that about 25% of patients taking Rezdiffra are also taking GLP-1 drugs, and half of the patients have tried using GLP-1 drugs in the past.
Another factor is the growing use of Tirzepatide, GLP-1- and GIP receptor-targeted peptides for Eli Lilly, as a sales of Mounjaro for type 2 diabetes, and Zepbough for weight management. Smith said it is unlikely that doctors will convert patients who have taken one of these Eli Lilly drugs to Novo Nordisk's products simply because of its dirt approval. For these patients, Rezdiffra will be the drug of choice added on top of Tirzepatide. That is, Eli Lilly is preparing for a three-stage test with Tirzepatide and Retatrutide Mash, a peptide that goes through three goals.
Mash (formerly known as non-alcoholic steatohepatitis or NASH) has been a difficult instruction for drug developers over the years. Genfit and interceptor drugs are biotechnology that encounter clinical trials and regulatory setbacks in metabolic diseases. But Leerink's Smith said the FDA nodded in MASH, labeled with a label consistent with the drug's clinical trial experience, Bolsters' confidence in the accelerated approval pathway for this indication. Leerink saw the latest Wegovy approval with positive readings for other drugs in late development of MASH.
Akero Therapeutics is currently in a 3-stage test using Efruxifermin, a fusion protein designed to mimic FGF21, a protein in the body called energy consumption and fat metabolism. The biotechnology has reported phase 2 results, showing this weekly MET trial target, showing improvements in MASH measures over 96 weeks. More detailed results were published last week in the Lancet magazine. 89BIO is also using the engineering version of FGF21, Pegozafermin, for 3-stage testing. Sagimet Biosciences takes a different approach with Denifanstat, an oral small molecule inhibitor of fatty acid synthase (FASN).
“Moving forward, we are inspired by the consistency of FDA labels, the timely nature of accelerated approvals, and the gradual view of non-invasive testing (NITS), which are changing the perceived difficulty of the regulatory pathway, as well as clinical and commercial Mash Landscape,” Smith said.
Photo: Michael Siluk/UCG/Universal Images group, via Getty Images
