GLP-1s May Protect Against Progression to Cirrhosis in MASLD

TOPLINE:

For patients with metabolic dysfunction–associated steatotic liver disease (MASLD) and diabetes, treatment with a glucagon-like peptide 1 receptor agonist (GLP-1 RA) may protect against progression to cirrhosis and mortality; however, the protective benefits do not extend to patients who already have cirrhosis, a new study found.

METHODOLOGY:

• GLP-1 RAs reduce liver inflammation in patients with MASLD, leading the researchers to study whether their use lowers the incidence of cirrhosis and its complications.
• Using Veterans Health Administration (VHA) data, they identified 16,058 patients with MASLD and type 2 diabetes who initiated a GLP-1 RA between 2006 and 2022 and an equal number of propensity score–matched patients who initiated a dipeptidyl peptidase 4 (DPP-4) inhibitor. Overall, 14,606 patients did not have cirrhosis and 1452 had cirrhosis.
• The primary outcome was progression to cirrhosis in those without cirrhosis and a composite of cirrhosis complications in those with cirrhosis. Secondary outcomes in both groups included decompensation, hepatocellular cancer (HCC), and all-cause mortality.

TAKEAWAY:

• In patients without cirrhosis, GLP-1 RA use was associated with a 14% lower risk of developing cirrhosis than DPP-4 inhibitor use (9.98 vs 11.1 events per 1000 person-years).
• In this group, GLP-1 RA use vs DPP-4 inhibitor use was also associated with a 22% lower risk for the composite of cirrhosis complications, a 25% lower risk for decompensated cirrhosis, and a 11% reduced risk for both HCC and all-cause mortality.
• In patients with preexisting cirrhosis, GLP-1 RA use didn’t provide a protective benefit over DPP-4 inhibitor use for the composite of cirrhosis complications (HR, 1.18), decompensated cirrhosis (HR, 1.14), or HCC (HR, 1.41). The HR for all-cause mortality was 0.88.
• After stratification by specific GLP-1 RAs, semaglutide was associated with a lower risk for progression to cirrhosis, although with wide confidence intervals.

IN PRACTICE:

This large study of patients with MASLD and diabetes but without cirrhosis revealed “protective associations between GLP-1 RA use and subsequent development of cirrhosis, cirrhosis complications, and overall mortality. This chemopreventive activity became apparent 18-24 months after treatment initiation and increased over time,” the authors wrote. The lack of benefit in patients with established cirrhosis highlights “the potential consequences of delaying treatment — either by lack of access or by patient or healthcare professional choice — on subsequent risk of cirrhosis complications.”

SOURCE:

The study, with first author Fasiha Kanwal, MD, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, was published online in JAMA Internal Medicine.

LIMITATIONS:

The study population was predominantly male veterans, and the follow-up period was relatively short. The potential for residual confounding and misclassification exists. Some outcomes may have been missed if patients sought care outside the VHA.

DISCLOSURES:

The study was supported by the National Cancer Institute and in part by grants from the National Institutes of Health and the Cancer Prevention and Research Institute of Texas. Author disclosures are available with the full text of the article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.