@article{7caa1a23b9ea48cead25950283256336,
title = "Cancer outcomes and all-cause mortality in adults allocated to metformin: Systematic review and collaborative meta-analysis of randomised clinical trials",
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 2statistics 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",
author = "Stevens, {R. J.} and R. Ali and Bankhead, {C. R.} and Bethel, {M. A.} and Cairns, {B. J.} and Camisasca, {R. P.} and Crowe, {F. L.} and Farmer, {A. J.} and S. Harrison and Hirst, {J. A.} and P. Home and Kahn, {S. E.} and McLellan, {J. H.} and R. Perera and A. Pl{\"u}ddemann and A. Ramachandran and Roberts, {N. W.} and Rose, {P. W.} and A. Schweizer and G. Viberti and Holman, {R. R.}",
note = "Funding Information: Duality of interest R. Ali has received grants and honoraria from GlaxoSmithKline and sanofi-aventis for research and educational activities in relation to cancer. M. A. Bethel receives research funding from Novartis and Bayer. Her department receives funding in support of research from Merck, Lilly and Amylin. R. P. Camisasca is currently a Takeda Global Research and Development Centre employee with the qualification of Group Medical Director, Diabetes and Metabolism. Funding Information: Funding The funding for the individual studies has been listed previously. Administrative support for the systematic review was funded by Diabetes UK (grant number 10/00040002). Funding Information: A. J. Farmer has received funding for travel to meetings in the past 12 months from Pfizer and sanofi-aventis, and his department has received funding from sanofi-aventis and Pfizer in payment for consultancy, but he has no personal interest in this funding. P. Home, for himself or on behalf of institutions with which he is associated, receives funding from manufacturers of most glucose-lowering products, including metformin and its competitors (sulfonylureas, insulins, DPP-4 inhibitors, and thiazolidinediones), for his research, educational and advisory activities. S. E. Kahn has received grant and/or consulting fees from Glaxo-SmithKline and Novartis. G. Viberti has, in the past, received consulting fees, grant support and lecture fees from, and has an equity interest in, GlaxoSmithKline; received consulting fees, grant support and lecture fees from Novartis; received consulting and lecture fees from Daiichi Sankyo and Speedel; and received grant support from Pfizer. He is now retired and as such no longer has any conflicts of interest. A. Schweizer is employed by and owns shares in Novartis. P. W. Rose is a partner in Primary Medical Education LLP. R. R. Holman has, in the last 12 months, received research support from Amylin, Bayer, Merck and Novartis; attended advisory boards with Amylin, Lilly, Merck, Novartis and Novo Nordisk; and given lectures supported by Bayer, Lilly, Merck and Novo Nordisk. R. J. Stevens, C. R. Bankhead, F. L. Crowe, B. J. Cairns, S. Harrison, J. A. Hirst, J. McLellan, R. Perera, A. Pl{\"u}ddemann, A. Ramachandran and N. W. Roberts have no conflicts to declare.",
year = "2012",
month = oct,
doi = "10.1007/s00125-012-2653-7",
language = "English (US)",
volume = "55",
pages = "2593--2603",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "10",
}