Metabolic dysfunction-associated steatotic liver disease affects approximately 70% of patients with T2DM and represents a major risk factor for HCC. A comprehensive meta-analysis, published in Cancer Medicine, evaluated the association between GLP-1RA use and HCC incidence, with attention to comparator therapies and liver disease status.

Nine cohort studies were included, encompassing 2,283,835 total patients, with 1,012,482 patients contributing to analyzed cohorts. Studies compared HCC incidence between GLP-1RA users and nonusers with T2DM. Random-effects meta-analysis, network meta-analysis, and meta-regression were performed, with heterogeneity explored through stratified analyses and quantitative bias assessment.

GLP-1RA use was associated with a 42% reduction in HCC risk, with a pooled hazard ratio of 0.60 (95% confidence interval 0.41 to 0.88; I² 86.2%). Effect size varied by comparator. Risk reduction was strongest versus insulin (hazard ratio 0.29; 95% confidence interval 0.13 to 0.67), and more modest versus oral glucose-lowering agents or no treatment. Meta-regression identified insulin as the primary contributor to between-study heterogeneity, accounting for 55% of the variance.

Benefit was greatest among patients without cirrhosis, with a hazard ratio of 0.41 (95% confidence interval 0.29 to 0.58). Network meta-analysis ranked GLP-1RAs highest for HCC prevention, with a surface under the cumulative ranking curve of 0.89, while insulin ranked lowest at 0.08. The estimated number needed to treat ranged from 24 to 476. These findings indicate that GLP-1RAs are associated with substantial HCC risk reduction in T2DM, supporting preferential use over insulin in patients at increased HCC risk.