GLP-1 Receptor Agonists Linked to Reduced Risk of Cirrhosis Progression in Early-Stage Metabolic Liver Disease

A recent cohort study has revealed potential benefits of GLP-1 receptor agonists (GLP-1 RAs) in managing metabolic dysfunction-associated steatotic liver disease (MASLD), a liver condition closely tied to metabolic disorders like type 2 diabetes. The study indicates that GLP-1 RAs may significantly lower the risk of progression to cirrhosis and related complications in early-stage MASLD.

However, the researchers noted that these protective benefits were not observed in patients who already had cirrhosis, underscoring the importance of early treatment. The findings were published in JAMA Internal Medicine on September 16, 2024.

Formerly known as non-alcoholic fatty liver disease (NAFLD), MASLD refers to liver conditions caused by metabolic dysfunction, which, if left untreated, can lead to cirrhosis—a severe condition characterized by liver scarring. GLP-1 RAs have been shown to improve liver inflammation in MASLD patients.

Dr. Fasiha Kanwal from Baylor College of Medicine and colleagues aimed to assess whether GLP-1 RAs reduce the risk of cirrhosis and its complications, such as decompensation and hepatocellular carcinoma (HCC), in MASLD patients. To do this, they conducted a retrospective cohort study using data from the Veterans Health Administration and Central Cancer Registry.

The study involved patients with MASLD and diabetes treated at 130 Veterans Health Administration hospitals. Patients who started using either GLP-1 RAs or dipeptidyl peptidase 4 inhibitors (DPP-4i) between January 2006 and June 2022 were followed until December 2022. GLP-1 RA users were matched 1:1 with DPP-4i users, and analyses were conducted separately for patients with and without cirrhosis at the start.

Key findings include:

• Among 16,058 patients who started GLP-1 RAs, 14,606 did not have cirrhosis (mean age: 60.56 years), while 1,452 had cirrhosis (mean age: 66.99 years) at baseline.

• GLP-1 RA users without cirrhosis showed a lower risk of cirrhosis progression compared to DPP-4i users (9.98 vs. 11.10 events per 1,000 person-years; HR: 0.86).

• Similar results were found for cirrhosis complications and mortality, with GLP-1 RA users showing reduced risk compared to DPP-4i users.

• No significant associations were observed in patients who already had cirrhosis.

• The researchers concluded that if these findings are confirmed by clinical trials, GLP-1 RAs could become a promising preventive treatment for cirrhosis and its complications in patients with MASLD and diabetes.