title: Does Metformin Reduce Cancer Risks? Methodologic Considerations.
abstract: The substantial burden of cancer and diabetes and the association between the two conditions has been a motivation for researchers to look for targeted strategies that can simultaneously affect both diseases and reduce their overlapping burden. In the absence of randomized clinical trials, researchers have taken advantage of the availability and richness of administrative databases and electronic medical records to investigate the effects of drugs on cancer risk among diabetic individuals. The majority of these studies suggest that metformin could potentially reduce cancer risk. However, the validity of this purported reduction in cancer risk is limited by several methodological flaws either in the study design or in the analysis. Whether metformin use decreases cancer risk relies heavily on the availability of valid data sources with complete information on confounders, accurate assessment of drug use, appropriate study design, and robust analytical techniques. The majority of the observational studies assessing the association between metformin and cancer risk suffer from methodological shortcomings and efforts to address these issues have been incomplete. Future investigations on the association between metformin and cancer risk should clearly address the methodological issues due to confounding by indication, prevalent user bias, and time-related biases. Although the proposed strategies do not guarantee a bias-free estimate for the association between metformin and cancer, they will reduce synthesis of and reporting of erroneous results.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Asieh
authors.initials: A
authors.lastname: Golozar
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Shuiqing
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Joeseph A
authors.initials: JA
authors.lastname: Lin
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.|The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Peairs
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. hyeh1@jhmi.edu.|Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. hyeh1@jhmi.edu.|The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. hyeh1@jhmi.edu.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, 2024 E. Monument St, Suite 2-500, Baltimore, MD, 21205, USA. hyeh1@jhmi.edu.
authors.forename: Hsin-Chieh
authors.initials: HC
authors.lastname: Yeh
mesh_terms: D000818:Animals; D015982:Bias; D048909:Diabetes Complications; D003920:Diabetes Mellitus; D006801:Humans; D008687:Metformin / Q000627:therapeutic use*; D009369:Neoplasms / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D064887:Observational Studies as Topic; D012307:Risk Factors
chemical_list: D008687:Metformin
keywords: Bias; Cancer; Confounding; Incidence; Metformin; Observational studies; Time-related bias