Over the last decade, about one in five people with metabolic dysfunction-associated steatohepatitis (MASH) and compensated cirrhosis were prescribed a GLP-1 receptor agonist, according to a study presented at the AASLD Liver Meeting.

 

As GLP-1 drugs, such as semaglutide (Ozempic or  Wegovy) and tirzepatide (Mounjaro or Zepbound) continue to grow in popularity, their benefits are being observed beyond obesity and diabetes.

 

The new findings suggest that GLP-1 use is rising among people with MASH and compensated cirrhosis (a milder form). Researchers encourage considering GLP-1s in clinical trial designs and treatment strategies for people with MASH.

 

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form, MASH, are responsible for a growing proportion of advanced liver disease worldwide. Around a third of people in the United States have MASLD, and about 5% have MASH. Over time, the buildup of fat in the liver can lead to serious complications, including cirrhosis and liver cancer.

Fatty liver disease often occurs in people with obesity, type 2 diabetes and other metabolic conditions. With only two approved medications, management still largely depends on lifestyle changes such as weight loss and exercise.

 

Two new studies led by Steve Gao, MD, PhD, and colleagues at Gilead Sciences investigated trends in GLP-1 use among people with MASH and compensated cirrhosis, Healio reported.

 

One cross-sectional study included about 91,800 people with MASH and compensated cirrhosis. Nearly 60% had type 2 diabetes, and about 62% had obesity. Between 2015 and 2024, 19.3% had at least one pharmacy claim for a GLP-1 drug.

 

GLP-1 use has steadily increased among people with MASH and compensated cirrhosis since 2018; the largest shift was seen from 2022 (11.2%) to 2024 (18.3%).

 

“This seems to suggest a significant shift in clinical practice, likely driven by the approval of newer GLP-1RAs and growing recognition of their benefits in managing comorbidities like type 2 diabetes and obesity,” Gao told Healio.

 

The second study involved a retrospective cohort of 8,282 people with MASH and compensated cirrhosis who had at least one pharmacy claim for GLP-1 within a year of compensated cirrhosis diagnosis between 2017 and 2024.

 

After 27 months, just over half (54%) of individuals discontinued their prescription for at least 135 days. The older GLP-1 agonist exenatide (Byetta or Bydureon) had the highest cumulative discontinuation rate of about 82.6% and semaglutide had the lowest at 60.7%.

 

Ozempic and Trulicity (dulaglutide) had the highest reinitiation rates, and the most common changes were from Trulicity or Victoza (liraglutide) to Ozempic and from Ozempic to Trulicity or Mounjaro.

 

“The high prevalence of GLP-1 use among patients with advanced MASH and comorbidities such as diabetes and obesity also highlights the importance of considering GLP-1 as part of combination therapies in the development of new treatment strategies and clinical trial designs for this population,” Gao said.

 

In related news, the Food and Drug Administration recently granted accelerated approval of Wegovy in conjunction with a reduced-calorie diet and exercise for people with MASH who have moderate to advanced liver fibrosis but have not yet developed cirrhosis. It is the second medication—and the first GLP-1 agonist—to gain approval for fatty liver disease.

 

The accelerated approval is supported by results from the Phase III ESSENCE trial, which showed that nearly two thirds of participants who received weekly injections of Wegovy experienced MASH resolution without worsening fibrosis, while more than a third showed fibrosis improvement without worsening MASH.

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