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. 2019 Jun;8(6):3206-3215.
doi: 10.1002/cam4.2142. Epub 2019 Apr 16.

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

Chen-Pin Wang  1 , John Kuhn  2 , Dimpy P Shah  1   3 , Susanne Schmidt  1 , Yui-Wing F Lam  2 , Daniel MacCarthy  1 , Laura Tenner  4 , Amelie G Ramirez  1   3
Affiliations

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

Chen-Pin Wang et al. Cancer Med. 2019 Jun.

Abstract

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.

Keywords: disparity; hepatocellular carcinoma; metformin; type 2 diabetes.

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Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
AORs associated with HCC by race/ethnicity (aOR associated with metformin use was adjusted for covariates, inverse propensity scores weighting of metformin use for each race/ethnic group, and inverse propensity scores weighting of race/ethnicity group membership). aORs, adjusted odds ratios; HCC, hepatocellular carcinoma
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