Cancer outcomes and all-cause mortality in adults allocated to metformin

Systematic review and collaborative meta-analysis of randomised clinical trials

R. J. Stevens, Raghib 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 & 1 others R. R. Holman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2593-2603
Number of pages11
JournalDiabetologia
Volume55
Issue number10
DOIs
StatePublished - Oct 1 2012

Fingerprint

Metformin
Meta-Analysis
Randomized Controlled Trials
Mortality
Neoplasms
Publications
Placebos
Incidence
Observational Studies
Research Personnel
Glucose

Keywords

  • Meta-analysis
  • Metformin
  • Neoplasms
  • Systematic review

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Cancer outcomes and all-cause mortality in adults allocated to metformin : Systematic review and collaborative meta-analysis of randomised clinical trials. / Stevens, R. J.; Ali, Raghib; Bankhead, C. R.; Bethel, M. A.; Cairns, B. J.; Camisasca, R. P.; Crowe, F. L.; Farmer, A. J.; Harrison, S.; Hirst, J. A.; Home, P.; Kahn, S. E.; McLellan, J. H.; Perera, R.; Plüddemann, A.; Ramachandran, A.; Roberts, N. W.; Rose, P. W.; Schweizer, A.; Viberti, G.; Holman, R. R.

In: Diabetologia, Vol. 55, No. 10, 01.10.2012, p. 2593-2603.

Research output: Contribution to journalArticle

Stevens, RJ, Ali, R, Bankhead, CR, Bethel, MA, Cairns, BJ, Camisasca, RP, Crowe, FL, Farmer, AJ, Harrison, S, Hirst, JA, Home, P, Kahn, SE, McLellan, JH, Perera, R, Plüddemann, A, Ramachandran, A, Roberts, NW, Rose, PW, Schweizer, A, Viberti, G & Holman, RR 2012, 'Cancer outcomes and all-cause mortality in adults allocated to metformin: Systematic review and collaborative meta-analysis of randomised clinical trials', Diabetologia, vol. 55, no. 10, pp. 2593-2603. https://doi.org/10.1007/s00125-012-2653-7
Stevens, R. J. ; Ali, Raghib ; Bankhead, C. R. ; Bethel, M. A. ; Cairns, B. J. ; Camisasca, R. P. ; Crowe, F. L. ; Farmer, A. J. ; Harrison, S. ; Hirst, J. A. ; Home, P. ; Kahn, S. E. ; McLellan, J. H. ; Perera, R. ; Plüddemann, A. ; Ramachandran, A. ; Roberts, N. W. ; Rose, P. W. ; Schweizer, A. ; Viberti, G. ; Holman, R. R. / Cancer outcomes and all-cause mortality in adults allocated to metformin : Systematic review and collaborative meta-analysis of randomised clinical trials. In: Diabetologia. 2012 ; Vol. 55, No. 10. pp. 2593-2603.
@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 Raghib 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.}",
year = "2012",
month = "10",
day = "1",
doi = "10.1007/s00125-012-2653-7",
language = "English (US)",
volume = "55",
pages = "2593--2603",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "10",

}

TY - JOUR

T1 - Cancer outcomes and all-cause mortality in adults allocated to metformin

T2 - Systematic review and collaborative meta-analysis of randomised clinical trials

AU - Stevens, R. J.

AU - Ali, Raghib

AU - Bankhead, C. R.

AU - Bethel, M. A.

AU - Cairns, B. J.

AU - Camisasca, R. P.

AU - Crowe, F. L.

AU - Farmer, A. J.

AU - Harrison, S.

AU - Hirst, J. A.

AU - Home, P.

AU - Kahn, S. E.

AU - McLellan, J. H.

AU - Perera, R.

AU - Plüddemann, A.

AU - Ramachandran, A.

AU - Roberts, N. W.

AU - Rose, P. W.

AU - Schweizer, A.

AU - Viberti, G.

AU - Holman, R. R.

PY - 2012/10/1

Y1 - 2012/10/1

N2 - 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.

AB - 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.

KW - Meta-analysis

KW - Metformin

KW - Neoplasms

KW - Systematic review

UR - http://www.scopus.com/inward/record.url?scp=84866138849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866138849&partnerID=8YFLogxK

U2 - 10.1007/s00125-012-2653-7

DO - 10.1007/s00125-012-2653-7

M3 - Article

VL - 55

SP - 2593

EP - 2603

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 10

ER -