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

Authors: R.J. Stevens, R. Ali, C.R. Bankhead, M.A. Bethel, B.J. Cairns, R.P. Camisasca, F.L. Crowe, A.J. Farmer, S.Harrison, J.A. Hirst, P. Home, S.E. Kahn, J.H. McLellan, R. Perera, A. Plüddemann, A. Ramachandran, N.W. Roberts, P.W. Rose, A. Schweizer, G. Viberti, R.R. Holman

Reference: Diabetologia 55(10):2593-2603.

Full text: [Full text] [Erratum]


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

Methods RCTs comparing metformin with active glucoselowering 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 I2 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

Keywords. Meta-analysis, Metformin, Neoplasms, Systematic review

Acknowledgement. We are grateful to the staff of the individual studies for their assistance in collating the data for analysis.

© 2002-2017 Benjamin J. Cairns: e-mail ; ph +44 1865 289673 ;
Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, U.K.