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Int J Cancer. 2016 Apr 15;138(8):1915-27. doi: 10.1002/ijc.29944. Epub 2015 Dec 15.

Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women's health initiative.

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Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY.
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA.
Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
Center for Health Research, Kaiser Permanente Northwest, Portland, OR.
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Department of Preventive Medicine and Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
Department of Epidemiology and Environment Health, State University of New York at Buffalo, Buffalo, NY.
Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, IN.


Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p < 0.001) and of several site-specific cancers (HR, 1.2-1.4, and up to over twofold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p < 0.001). There was no overall difference in cancer incidence by diabetes therapy (p = 0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 vs. 1.45; p = 0.007) and for breast cancer (HRs, 0.50 vs. 1.29; p = 0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer.


diabetes; incidence; invasive cancer; metformin; mortality

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