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Diabetologia. 2012 Oct;55(10):2593-2603. doi: 10.1007/s00125-012-2653-7. Epub 2012 Aug 10.

Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.

Author information

Department of Primary Care Health Sciences, University of Oxford, Woodstock Road, Oxford, OX2 6GG, UK.
Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
Department of Primary Care Health Sciences, University of Oxford, Woodstock Road, Oxford, OX2 6GG, UK.
Diabetes Trials Unit, Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.
TGRD Europe, Takeda Pharmaceutical Company, London, UK.
ICM-Diabetes, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, WA, USA.
India Diabetes Research Foundation, Dr A. Ramachandran's Diabetes Hospitals, Egmore, Chennai, India.
Novartis Pharma, Basel, Switzerland.
Unit for Metabolic Medicine, School of Medicine, King's College London, London, UK.

Erratum in

  • Diabetologia. 2012 Dec;55(12):3399-400.



Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs).


RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis.


Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials.


Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

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