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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

1
Department of Primary Care Health Sciences, University of Oxford, Woodstock Road, Oxford, OX2 6GG, UK. richard.stevens@phc.ox.ac.uk.
2
Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
3
Department of Primary Care Health Sciences, University of Oxford, Woodstock Road, Oxford, OX2 6GG, UK.
4
Diabetes Trials Unit, Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.
5
TGRD Europe, Takeda Pharmaceutical Company, London, UK.
6
ICM-Diabetes, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
7
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, WA, USA.
8
India Diabetes Research Foundation, Dr A. Ramachandran's Diabetes Hospitals, Egmore, Chennai, India.
9
Novartis Pharma, Basel, Switzerland.
10
Unit for Metabolic Medicine, School of Medicine, King's College London, London, UK.

Erratum in

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

Abstract

AIMS/HYPOTHESIS:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS/INTERPRETATION:

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.

Comment in

PMID:
22875195
DOI:
10.1007/s00125-012-2653-7
[Indexed for MEDLINE]

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