By A.J. Hostetler 

Millions of Americans are unaware they have something dangerous happening inside their bodies — a silent type of liver disease called metabolic dysfunction-associated steatohepatitis or MASH. 

MASH is not caused by drinking alcohol, but by everyday problems like obesity, diabetes and eating too many unhealthy foods. As more people around the world gain weight or develop diabetes, more people are discovering too late that they have this condition. 

MASH begins with fat building up in the liver. Over time, that causes inflammation which can lead to scarring called fibrosis. If it gets worse, the scarring can turn into cirrhosis, a life-threatening form of scar tissue that stops the liver from working properly. 

For years, physicians could only recommend lifestyle changes, especially weight loss, as a treatment. Over the past decade, many potential therapies that seemed promising have failed in the long run. 

“There’s a huge graveyard of failed drugs,” said Amon Asgharpour, M.D., a transplant hepatologist at VCU Health affiliated with the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health. Asgharpour has served as a lead researcher for many potential liver disease therapies. 

In 2024, the first drug was approved by the U.S. Food ad Drug Administration to treat MASH. The Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at VCU actively participated in the clinical trial that led to this groundbreaking milestone for treating the condition. 

“We’re happy now that we have something approved by the FDA and more in the pipeline,” said Asgharpour, who co-authored a review of emerging MASH therapies with endocrinologist Priyanka Majety, M.D., of the Virginia Commonwealth University’s School of Medicine. 

“Identifying the disease drivers is a critical step toward developing effective treatments,” Majety said. “The possibility of additional FDA-approved therapies in the near future is certainly promising.” 

Several new treatments are far along in clinical trials and holding on to their promise. Some target fat buildup, others fight inflammation. Some are designed to break down the scar tissue itself. The common denominator among them all: the VCU liver institute’s involvement. Together, these studies mark the most serious effort yet to find a treatment for MASH before scaring leads to liver failure, cancer or death – and the liver institute is leading the way. 

FDA approves semaglutide for treating MASH with fibrosis 

The liver institute, under the leadership of its director Arun Sanyal, M.D., played a pivotal role in a groundbreaking international study on semaglutide, a GLP-1 receptor agonist found in weight loss drug Wegovy and Ozempic. It’s known to promote weight loss, improve blood sugar control and enhance metabolic health, and findings from VCU-led research show that semaglutide can halt and even reverse MASH. The study, as with most research testing the efficacy and safety of a drug, was funded by the semaglutide manufacturer Novo Nordisk. 

In August 2025, Wegovy was federally approved to treat MASH in adults with excessive scar tissue in the liver.  

Semaglutide is also being tested as a treatment when paired with other medications, cilofexor and firsocostat. That’s because a growing number of liver specialists now believe multiple medicines may need to be used at the same time to treat MASH. Each drug works in a different way, and early results suggest that these combinations may have a stronger effect on liver healing than any single drug alone. 

FGF21 analogs on the fast track to federal approval 

FGF21 analogs mimic a hormone the body already makes called fibroblast growth factor 21, or FGF21. This hormone helps regulate metabolism, reduce fat in the liver, and protect liver cells from damage.  

VCU researchers are involved in international clinical trials for two FGF21 analog drugs: efruxifermin and pegozafermin. They’re testing how effective they are in treating patients with MASH and have additional liver scarring from either fibrosis or cirrhosis, and so far, the results are promising. Both drugs have been shown to reverse liver scarring, reduce inflammation and improve blood sugar levels. 

Over about two years of treatment, efruxifermin helped 39% of patients with MASH and cirrhosis improve their liver scarring to the point that the severity of their diagnosis changed – one of the strongest results ever reported for a drug tested in people with advanced scarring.  

Pegozafermin’s clinical trial results were so strong that the FDA gave it a special “Breakthrough Therapy” designation for MASH with fibrosis in 2023 to expedite its development.  

Another weight loss drug that could help MASH patients 

In a study published last year, tirzepatide was shown to resolve MASH in nearly 62% of people who participated in a clinical trial. Tirzepatide is a compound in weight loss drugs Zepbound and Mounjaro. It’s a dual GIP/GLP-1 receptor co-agonist which means it can act on two separate hormones to treat type 2 diabetes and obesity. Tirzepatide is in a Phase 3 clinical trial.   

New therapy survodutide could offer hope for MASH with fibrosis patients 

VCU researchers are actively involved in clinical trials for survodutide, a dual glucagon/GLP-1 receptor agonist that controls hunger and satiety, allowing people to feel fuller after eating for longer. 

Survodutide has shown significant potential, with up to 83% of participants experiencing improvements in liver fat and inflammation, and no worsening of fibrosis. Sanyal described the drug as a possible “game-changer” for millions of people who both MASH with fibrosis and illnesses related to obesity. 

Retatrutide shows major liver fat reduction in clinical trial participants 

In another major study led by Sanyal, VCU researchers and teams from collaborating institutions are testing retatrutide, a triple receptor agonist targeting GIP, GLP-1, and glucagon receptors.  

Initial findings from clinical trials revealed that around 85% of obese participants with fatty liver disease experienced significant reduction in liver fat to the point that they would no longer be classified as having fatty liver disease. Retatrutide is currently in a Phase 3 clinical trial. 

Why prevention still matters for lifelong liver health 

Even as these new drugs offer hope, prevention remains essential. Doctors continue to recommend healthy eating, regular physical activity and weight loss for people at risk of developing MASH. Research shows that losing as little as 10% of body weight after one year can not only reduce liver fat and improve inflammation – it can reverse liver scarring and organ damage. 

For people who already have cirrhosis, these new drugs could be lifesaving and even prevent the need for a liver transplant. But for those with earlier stages of fatty liver disease – diet and exercise remain the first line of defense. 

Researchers believe that treatments for MASH cirrhosis are finally within reach. If the current clinical trials succeed, the first approved drugs to reverse – not just halt – fibrosis could arrive in just a few years. 

How could a drug for diabetes and obesity help heal the liver? Read more about the research into GLP-1s and liver disease.

See how VCU’s Stravitz-Sanyal Institute for Liver Disease and Metabolic Health is making an impact.