Cancer Causes & Control

, Volume 29, Issue 9, pp 823–832 | Cite as

Metformin use and incidence cancer risk: evidence for a selective protective effect against liver cancer

  • Harvey J. MurffEmail author
  • Christianne L. Roumie
  • Robert A. Greevy
  • Amber J. Hackstadt
  • Lucy E. D’Agostino McGowan
  • Adriana M. Hung
  • Carlos G. Grijalva
  • Marie R. Griffin
Original paper



Several observational studies suggest that metformin reduces incidence cancer risk; however, many of these studies suffer from time-related biases and several cancer outcomes have not been investigated due to small sample sizes.


We constructed a propensity score-matched retrospective cohort of 84,434 veterans newly prescribed metformin or a sulfonylurea as monotherapy. We used Cox proportional hazard regression to assess the association between metformin use compared to sulfonylurea use and incidence cancer risk for 10 solid tumors. We adjusted for clinical covariates including hemoglobin A1C, antihypertensive and lipid-lowering medications, and body mass index. Incidence cancers were defined by ICD-9-CM codes.


Among 42,217 new metformin users and 42,217 matched-new sulfonylurea users, we identified 2,575 incidence cancers. Metformin was inversely associated with liver cancer (adjusted hazard ratio [aHR] = 0.44, 95% CI 0.31, 0.64) compared to sulfonylurea. We found no association between metformin use and risk of incidence bladder, breast, colorectal, esophageal, gastric, lung, pancreatic, prostate, or renal cancer when compared to sulfonylurea use.


In this large cohort study that accounted for time-related biases, we observed no association between the use of metformin and most cancers; however, we found a strong inverse association between metformin and liver cancer. Randomized trials of metformin for prevention of liver cancer would be useful to verify these observations.


Diabetes mellitus Metformin Cancer Sulfonylureas 



This work was supported under Contract No. 290-05-0042 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. This project was additionally supported by National Institutes of Health (P20 DK090874-01) and in part by the by VA Clinical Science research and Development investigator-initiated grant CX000570-01 (Roumie). Dr. Murff was supported in part by R01CA143288 and R01CA160938 from the National Cancer Institute. Dr. Roumie was also supported in part by Center for Diabetes Translation Research P30DK092986. Dr. Hung (2-031-09S) was supported by a VA Career Development Award. Dr. Grijalva was supported in part by R01AG043471 from the National Institute on Aging. Support for Veterans Affairs/Centers for Medicare & Medicaid Services data was provided by the Department of Veterans Affairs, Veterans Affairs Health Services Research and Development Service, Veterans Affairs Information Resource Center (Project Nos. SDR 02-237 and 98-004).

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflicts of interest to disclose.

Supplementary material

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Harvey J. Murff
    • 1
    • 2
    • 5
    Email author
  • Christianne L. Roumie
    • 1
    • 2
  • Robert A. Greevy
    • 1
    • 3
  • Amber J. Hackstadt
    • 3
  • Lucy E. D’Agostino McGowan
    • 3
  • Adriana M. Hung
    • 1
    • 2
  • Carlos G. Grijalva
    • 1
    • 4
  • Marie R. Griffin
    • 1
    • 2
    • 4
  1. 1.Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center (GRECC), HSR&D CenterNashvilleUSA
  2. 2.Department of MedicineVanderbilt UniversityNashvilleUSA
  3. 3.Department of BiostatisticsVanderbilt UniversityNashvilleUSA
  4. 4.Department of Health PolicyVanderbilt UniversityNashvilleUSA
  5. 5.Vanderbilt University Medical CenterNashvilleUSA

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