Metformin use and the risk of liver cancer in a Swedish population-based cohort study

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ID: 314911
2026
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Abstract
Abstract Background It is uncertain whether medication with metformin decreases the risk of liver cancer. This study aimed to test the hypotheses that use of metformin decreases the risk of developing both main subtypes of liver cancer, ie, hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Methods This nationwide population-based cohort study included all individuals who had dispensed anti-diabetic medications between 2005 to 2018 in Sweden, except for those with a history of viral hepatitis. We assessed the associations between metformin use and the risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma by using Cox regression, adjusted for age, sex, calendar year, smoking-related diagnoses, alcohol-related diagnoses, non-alcoholic fatty liver disease, use of non-steroidal anti-inflammatory drugs, and use of statins. Results Among 744,173 participants, 526,859 (70.8%) were metformin users. During the follow-up of a median of 6.8 (maximum 13.5) years, 1,622 participants developed hepatocellular carcinoma and 319 developed intrahepatic cholangiocarcinoma. Metformin use was associated with a slightly increased risk of hepatocellular carcinoma (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.02 to 1.30), but a decreased risk in participants with a prior diagnosis of obesity (HR 0.56, 95% CI 0.34 to 0.90). No statistically significant association was observed for intrahepatic cholangiocarcinoma (HR 0.77, 95% CI 0.59 to 1.01). Conclusion This study found an increased risk of hepatocellular carcinoma associated with metformin use overall, while suggesting a decreased risk in individuals with obesity. No clear association was observed for intrahepatic cholangiocarcinoma.
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openalex_W7162290354 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Yongying Huang, Giola Santoni, Ernesto Sparrelid, Shao-Hua Xie
Journal jnci cancer spectrum
Year 2026
DOI
10.1093/jncics/pkag053
URL
https://doi.org/10.1093/jncics/pkag053
Keywords Keywords not found

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