Metformin modifies disparity in hepatocellular carcinoma incidence in men with type 2 diabetes but without chronic liver diseases

Background We assessed racial/ethnic disparity in hepatocellular carcinoma (HCC) incidence among men with type 2 diabetes (T2D) but without chronic liver diseases (CLD), and whether metformin use modified the disparity. Methods Study cohort: the nationwide Veterans Administration Health Care System electronic medical records among 40‐89 years old men with T2D; without CLD, cancer, cardiovascular or renal diseases previously; insulin and thiazolidinedione naive. Logistic regression analyses compared HCC incidence between race/ethnicity groups under no metformin use adjusted for covariates and inverse propensity score weights (IPSW) for race/ethnicity. The generalizability technique integrated with IPSW was incorporated to compare covariates adjusted odds ratios (aOR) of HCC associated with metformin use among race/ethnicity groups. Results Study cohort: N = 84 433; 79.47% non‐Hispanic white (NHW), 15.5% non‐Hispanic African American (NHAA), 5.03% Hispanics; 36.76% metformin users; follow‐up 6.10 ± 2.87 years; age 67.8 ± 9.8 years, HbA1c 6.57 ± 0.98%; 0.14% HCC cases. Under no metformin use, HCC incidence was lower for NHAA vs NHW (aOR = 0.60 [0.40‐0.92]), similar between NHW and Hispanics. Metformin was associated with reduced HCC risk: aOR = 0.57 (0.40‐0.81) for NHW; aOR = 0.35 (0.25‐0.47) for NHAA; aOR = 0.31 (0.22‐0.43) for Hispanics. Metformin dose >1000 mg/d was neutral for NHW; less effective for NHAA (P = 0.02); more effective for Hispanics (P = 0.002). Conclusions In men with T2D but without CLD nor metformin use, HCC incidence was lower for NHAA compared to NHW or Hispanics; similar between NHW and Hispanics. Metformin use reduced HCC risk and modified the race/ethnicity disparity. Impact Metformin's heterogeneous HCC prevention effect elucidates potential interventions to modify HCC disparity in patients with T2D. Metformin's heterogeneous effect on hepatocellular carcinoma (HCC) prevention elucidates potential intervention strategies to modify HCC disparity in patients with type 2 diabetes.