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Updated: Jan 8, 2026

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Published on: September 30, 2021
Glucagon-Like Peptide-1 Receptor Agonists and Hepatocellular Carcinoma Prevention: A Meta-Analysis and Clinical
Andrea Dalbeni1,2, Marco Vicardi1,2, Leonardo Antonio Natola1,2
1Unit of General Medicine C, Medicine Department, University of Verona and University and Hospital Trust (AOUI) of Verona, Verona, Italy.
Background & Aims:
While glucagon-like peptide-1 receptor agonists (GLP-1RAs) show promise for hepatoprotection in type 2 diabetes mellitus (T2DM), the magnitude of hepatocellular carcinoma (HCC) risk reduction and optimal patient selection remain unclear. This is particularly relevant given that metabolic dysfunction-associated steatotic liver disease (MASLD) affects 70% of patients with T2DM and represents a major HCC risk factor. We conducted a comprehensive meta-analysis to quantify GLP-1RA efficacy in HCC prevention and inform clinical implementation strategies.
Methods:
We systematically searched PubMed, Embase, and Web of Science through June 2025 for cohort studies comparing HCC incidence between GLP-1RA users and nonusers with T2DM. Random-effects meta-analysis, network meta-analysis, and meta-regression were performed. Heterogeneity was explored through stratified analyses and quantitative bias assessment.
Results:
Nine studies encompassing 2,283,835 total patients (analyzed cohorts: 1,012,482) were included. GLP-1RA use was associated with a 42% reduced HCC risk (pooled HR 0.60, 95% CI: 0.41-0.88; I2 = 86.2%). Effect magnitude varied significantly by comparator: versus insulin (HR 0.29, 95% CI: 0.13-0.67), versus oral agents (HR 0.81, 95% CI: 0.63-1.05), versus no treatment (HR 0.77, 95% CI: 0.52-1.14). Meta-regression identified insulin as comparator as the primary driver of heterogeneity, explaining 55% of the between-study variance. Benefits were greatest in patients without cirrhosis (HR 0.41, 95% CI: 0.29-0.58). Network meta-analysis ranked GLP-1RAs highest for HCC prevention (SUCRA 0.89), with insulin ranking lowest (0.08). The number needed to treat ranged from 24 to 476.
Conclusions:
GLP-1RAs substantially reduce HCC risk in T2DM, with benefits partly attributable to avoiding insulin's potential hepatotoxicity. These findings support the preferential use of GLP-1RAs over insulin in patients at HCC risk.
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