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Epidemiology/Health Services Research

Metformin Does Not Affect Cancer Risk: A Cohort Study in the U.K. Clinical Practice Research Datalink Analyzed Like an Intention-to-Treat Trial

  1. Konstantinos K. Tsilidis1,2⇑,
  2. Despoina Capothanassi1,
  3. Naomi E. Allen3,
  4. Evangelos C. Rizos4,
  5. David S. Lopez5,
  6. Karin van Veldhoven6,8,
  7. Carlotta Sacerdote7,
  8. Deborah Ashby9,
  9. Paolo Vineis6,7,
  10. Ioanna Tzoulaki1,6 and
  11. John P.A. Ioannidis10
  1. 1Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
  2. 2Cancer Epidemiology Unit, University of Oxford, Oxford, U.K.
  3. 3Clinical Trial Service Unit, University of Oxford, Oxford, U.K.
  4. 4Lipid Disorders Clinic, Department of Internal Medicine, University Hospital of Ioannina, Ioannina, Greece
  5. 5Division of Epidemiology, University of Texas School of Public Health, Houston, TX
  6. 6Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, U.K.
  7. 7Human Genetics Foundation (HuGeF), Turin, Italy
  8. 8University College London Institute of Child Health, Centre for Paediatric Epidemiology and Biostatistics, London, U.K.
  9. 9Imperial Clinical Trials Unit, School of Public Health, Imperial College London, St Mary's Hospital, London, U.K.
  10. 10Stanford Prevention Research Center, Department of Medicine; Department of Health Research and Policy, Stanford University School of Medicine; and Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA
  1. Corresponding author: Konstantinos K. Tsilidis, ktsilidi{at}cc.uoi.gr, ktsilidis{at}gmail.com.
Diabetes Care 2014 Sep; 37(9): 2522-2532. https://doi.org/10.2337/dc14-0584
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Abstract

OBJECTIVE Meta-analyses of epidemiologic studies have suggested that metformin may reduce cancer incidence, but randomized controlled trials did not support this hypothesis.

RESEARCH DESIGN AND METHODS A retrospective cohort study, Clinical Practice Research Datalink, was designed to investigate the association between use of metformin compared with other antidiabetes medications and cancer risk by emulating an intention-to-treat analysis as in a trial. A total of 95,820 participants with type 2 diabetes who started taking metformin and other oral antidiabetes medications within 12 months of their diagnosis (initiators) were followed up for first incident cancer diagnosis without regard to any subsequent changes in pharmacotherapy. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% CI.

RESULTS A total of 51,484 individuals (54%) were metformin initiators and 18,264 (19%) were sulfonylurea initiators, and 3,805 first incident cancers were diagnosed during a median follow-up time of 5.1 years. Compared with initiators of sulfonylurea, initiators of metformin had a similar incidence of total cancer (HR 0.96; 95% CI 0.89–1.04) and colorectal (HR 0.92; 95% CI 0.76–1.13), prostate (HR 1.02; 95% CI 0.83–1.25), lung (HR 0.85; 95% CI 0.68–1.07), or postmenopausal breast (HR 1.03; 95% CI 0.82–1.31) cancer or any other cancer.

CONCLUSIONS In this large study, individuals with diabetes who used metformin had a similar risk of developing cancer compared with those who used sulfonylureas.

Footnotes

  • This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc14-0584/-/DC1.

  • Received March 6, 2014.
  • Accepted April 24, 2014.
  • © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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Metformin Does Not Affect Cancer Risk: A Cohort Study in the U.K. Clinical Practice Research Datalink Analyzed Like an Intention-to-Treat Trial
Konstantinos K. Tsilidis, Despoina Capothanassi, Naomi E. Allen, Evangelos C. Rizos, David S. Lopez, Karin van Veldhoven, Carlotta Sacerdote, Deborah Ashby, Paolo Vineis, Ioanna Tzoulaki, John P.A. Ioannidis
Diabetes Care Sep 2014, 37 (9) 2522-2532; DOI: 10.2337/dc14-0584

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Metformin Does Not Affect Cancer Risk: A Cohort Study in the U.K. Clinical Practice Research Datalink Analyzed Like an Intention-to-Treat Trial
Konstantinos K. Tsilidis, Despoina Capothanassi, Naomi E. Allen, Evangelos C. Rizos, David S. Lopez, Karin van Veldhoven, Carlotta Sacerdote, Deborah Ashby, Paolo Vineis, Ioanna Tzoulaki, John P.A. Ioannidis
Diabetes Care Sep 2014, 37 (9) 2522-2532; DOI: 10.2337/dc14-0584
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