GLP-1 Agonists Show Promise in Treating Patients with MASLD and Diabetes

Glucagon-like peptide-1 (GLP-1) agonists reduced the risk of cirrhosis and hepatocellular carcinoma (HCC) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and Type 2 diabetes, according to a new retrospective cohort study presented by Fasiha Kanwal, MD, MSHS, professor and section chief of gastroenterology at Baylor College of Medicine during Digestive Disease Week® (DDW) 2024.

“We know that MASLD and diabetes increase the risk of cirrhosis and HCC. Growing evidence suggests that GLP-1 receptor agonists have a beneficial effect on liver inflammation, but whether that leads to improved outcomes is unknown,” says Dr. Kanwal. “This study shows that GLP-1 receptor agonists may actually reduce the risk of liver outcomes in patients with MASLD.”

The study was a retrospective cohort of patients in the U.S. Veterans Affairs healthcare system. The study population consisted of 23,670 adults with MASLD and Type 2 diabetes on a GLP-1 receptor agonist, along with nearly 170,000 controls — patients with MASLD and Type 2 diabetes not on a GLP-1 receptor agonist.

Of the patients on GLP-1 receptor agonists, 70% were on semaglutide. Thirteen percent were on liraglutide, while 17% were on both agents.

Key results after a median follow-up of 20 months include:

Patients on a GLP-1 receptor agonist had a lower annual incidence of cirrhosis (0.81%) than those not on a GLP-1 agonist (1.9%). GLP-1 receptor agonists were associated with a lower risk of HCC. (annual incidence 0.02% versus 0.04%)
There was no statistically significant difference in the risk of HCC between GLP-1 receptor agonist users and non-users with cirrhosis. (annual incidence 0.36% versus 0.51%)

MASLD is a new term adopted by several multinational liver societies in 2023 to replace nonalcoholic fatty liver disease (NAFLD). The new nomenclature now defines liver disease based on what is causing it — instead of what isn’t.

“The term MASLD focuses on the underlying disease pathophysiology, namely factors associated with cardiometabolic risk — obesity, high blood pressure and high glucose levels,” said Dr. Kanwal. “This could pave the way for new research on targeting the mechanisms behind MASLD.”

Dr. Kanwal notes that the prevalence of MASLD is expected to increase dramatically in coming decades. A 2023 systematic review estimated the global prevalence of NAFLD (the study was conducted before the name change) was 30% — and rising.

“With the increasing prevalence of MASLD and the advent of new non-invasive diagnostics, the management of MASLD must expand beyond the hepatologist to gastroenterologists, endocrinologists and primary care providers,” says Dr. Kanwal. “Having therapies that these specialties are already comfortable with that address not only cardiometabolic risk but also liver-related outcomes could simplify the management of these patients.”

She hopes that this study will encourage randomized, prospective trials to investigate the effects of GLP-1 receptor agonists on patients with MASLD.

Dr. Kanwal’s oral presentation, “Association of glucagon-like peptide-1 agonists with cirrhosis and hepatocellular cancer in metabolic dysfunction associated steatotic liver disease (MASLD)” on Saturday, May 18, at 8 a.m. EDT is part of the AASLD Presidential Plenary.

If you’re attending DDW, your registration includes access to a recording of this session, available to watch at your convenience until May 16, 2025. Session captures will be released 24 hours after the session ends. Non-attendees can also purchase access to DDW On Demand to watch session recordings starting June 5.