Association of GLP1-Receptor Agonists with Risk of Hepatocellular Carcinoma: A Retrospective Cohort Study

Joane Titus, Vinay Katukuri, Moheb Boktor and Ishak A. Mansi ()
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Joane Titus: University of Central Florida
Vinay Katukuri: University of Central Florida
Moheb Boktor: University of Texas Southwestern Medical Center
Ishak A. Mansi: University of Central Florida

Drug Safety, 2025, vol. 48, issue 10, No 3, 1089-1101

Abstract: Abstract Background The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has exponentially increased owing to their favorable cardio-renal-metabolic effects. Some studies have raised concerns about a potential association between GLP-1RA use and malignancy. This study aimed to examine the association between GLP-1RA use and risk of hepatocellular carcinoma (HCC). Methods This retrospective propensity score (PS)-matched cohort study used data from the Veterans Health Administration (years 2006–2021). Using a new-user active comparator design, the study included adults who initiated a GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP4i) as an active comparator and had no prior history of HCC or liver transplantation. The primary outcome was incident HCC. We developed a PS that included 133 variables encompassing diabetes severity, hepatic conditions, liver disease scores, vital signs, laboratory investigations, comorbidity scores, and use of other medication classes. Results Of 147,969 GLP-1RA and 263,664 DPP4i users, 100,248 pairs of GLP-1RA and DPP4i users were PS-matched. Hepatocellular carcinoma occurred in 302 (0.30%) GLP-1RA users and in 230 (0.23%) DPP4i users (odds ratio [OR]: 1.31, 95% confidence interval [95% CI]: 1.11–1.56). Secondary analysis, which stratified patients by duration of medication use, showed an increased risk of HCC in association with GLP-1RA use > 6 months, but similar HCC risk if medication use was

Date: 2025
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DOI: 10.1007/s40264-025-01558-1

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