Unclear evidence on whether metformin reduces the risk of cancer in type 2 diabetes

Previous observational studies have suggested that use of metformin is associated with a reduction in the risk of cancer. This systematic review set out to clarify this question by incorporating the findings of recent trials.

Clinical question:

In people with type 2 diabetes taking metformin, what is the risk of cancer of any type?

The review looked at incidence of new cases of cancer of all types, and mortality from cancer.

The evidence:

24 articles were found that met the inclusion criteria.  This included three RCTs;  the remainder were observational studies (case-control or cohort studies).  Not all studies reported the same outcomes;  mortality was only reported in six studies whilst cancer incidence was reported in ten.

When the data were combined, the pooled risk ratios (RRs) for metformin versus non-metformin users were:

  • 0.66 (95% CI:  0.49–0.88) for all-cancer mortality,
  • 0.67 (95% CI:0.53–0.85) for all-cancer incidence.

Note that when observational studies were excluded from the analysis, no benefit was found.

Appraisal hints:

Users of this research should consider:

  • The search did not include EMBASE.  There is a chance that the reviewers missed important evidence.
  • There was blind, independent assessment of study quality and data extraction.
  • The review included observational studies, which are more susceptible to bias than experimental RCTs.
  • There is a lot of scope for confounding in observational studies, where patients may be at radically different stages of illness when they are receiving metformin compared with when they receive other treatments.
  • There is a need for larger-scale prospective and ideally randomised studies to establish whether metformin does prevent cancer in type 2 diabetes.


The full text of this review is available for free from the Public Library of Science:

Noto H, Goto A, Tsujimoto T, Noda M. Cancer Risk in Diabetic Patients Treated with Metformin: A Systematic Review and Meta-analysis. PLoS One. 2012;7(3):e33411. Epub 2012 Mar 20.

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I am an information scientist with an interest in making knowledge from systematic research more accessible to people who need it. This means you. I've been attempting this in the area of Evidence-Based Health Care since 1995. So far the results have been mixed. For some reason we expected busy clinicians to search databases and appraise papers instead of seeing patients. We also expected publishers to make the research freely available to the people who paid for it.. Ha! Hence The National Elf service.

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