Background: Whether metformin may reduce hepatocellular carcinoma (HCC) risk requires confirmation.

Methods: Newly diagnosed type 2 diabetes patients during 1999-20with 2 or more prescriptions of antidiabetic drugs were enrolled from the Taiwan’s National Health Insurance. A total of 173917 ever users and 21900 never users of metformin were identified (unmatched cohort). A 1:1 matched-pairs cohort of 21900 ever users and 21900 never users based on propensity score was created. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using PS. Additionally, the interactions with aspirin and statin were evaluated.

Results: In the unmatched cohort, 619 never users and 2642 ever users developed HCC, with respective incidence of 668.0 and 330.7 per 100,000 person-years and overall hazard ratio of 0.49 (95% confidence interval: 0.45-0.54). The hazard ratio for the first (<25.7 months), second (25.7-56.9 months) and third (>56.9 months) tertile of cumulative duration of metformin therapy was 0.89 (0.81-0.98), 0.50 (0.46-0.56) and 0.23 (0.21-0.26), respectively. Analyses in the matched cohort showed an overall hazard ratio of 0.69 (0.62-0.78) and the hazard ratio for the respective tertile was 1.28 (1.10-1.50), 0.68 (0.57-0.82) and 0.35 (0.29-0.44). A significant interaction with metformin was observed for aspirin and statin.

Conclusions: Metformin is associated with a reduced risk of HCC in a dose-response pattern. Users of both metformin and aspirin or statin have the lowest risk.


C. Tseng: None.

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