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

Author

Listed:
  • Joane Titus

    (University of Central Florida
    University of Central Florida College of Medicine/HCA Florida Healthcare GME)

  • Vinay Katukuri

    (University of Central Florida
    University of Central Florida College of Medicine/HCA Florida Healthcare GME)

  • Moheb Boktor

    (University of Texas Southwestern Medical Center)

  • Ishak A. Mansi

    (University of Central Florida
    Orlando VA Medical Center)

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

Suggested Citation

  • Joane Titus & Vinay Katukuri & Moheb Boktor & Ishak A. Mansi, 2025. "Association of GLP1-Receptor Agonists with Risk of Hepatocellular Carcinoma: A Retrospective Cohort Study," Drug Safety, Springer, vol. 48(10), pages 1089-1101, October.
    • Handle: RePEc:spr:drugsa:v:48:y:2025:i:10:d:10.1007_s40264-025-01558-1
    DOI: 10.1007/s40264-025-01558-1
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