Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.
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/usu...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1797075084074024960 |
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| author | Stevens, R Ali, R Bankhead, C Bethel, M Cairns, B Camisasca, R Crowe, F Farmer, A Harrison, S Hirst, J Home, P Kahn, SE Mclellan, J Perera, R Plüddemann, A Ramachandran, A Roberts, N Rose, P Schweizer, A Viberti, G Holman, R |
| author_facet | Stevens, R Ali, R Bankhead, C Bethel, M Cairns, B Camisasca, R Crowe, F Farmer, A Harrison, S Hirst, J Home, P Kahn, SE Mclellan, J Perera, R Plüddemann, A Ramachandran, A Roberts, N Rose, P Schweizer, A Viberti, G Holman, R |
| author_sort | Stevens, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:45:16Z |
| format | Journal article |
| id | oxford-uuid:70b06e20-eacb-457d-a108-e715af07dc8d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:45:16Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:70b06e20-eacb-457d-a108-e715af07dc8d2022-03-26T19:38:49ZCancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:70b06e20-eacb-457d-a108-e715af07dc8dEnglishSymplectic Elements at Oxford2012Stevens, RAli, RBankhead, CBethel, MCairns, BCamisasca, RCrowe, FFarmer, AHarrison, SHirst, JHome, PKahn, SEMclellan, JPerera, RPlüddemann, ARamachandran, ARoberts, NRose, PSchweizer, AViberti, GHolman, RAIMS/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. |
| spellingShingle | Stevens, R Ali, R Bankhead, C Bethel, M Cairns, B Camisasca, R Crowe, F Farmer, A Harrison, S Hirst, J Home, P Kahn, SE Mclellan, J Perera, R Plüddemann, A Ramachandran, A Roberts, N Rose, P Schweizer, A Viberti, G Holman, R Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. |
| title | Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. |
| title_full | Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. |
| title_fullStr | Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. |
| title_full_unstemmed | Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. |
| title_short | Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. |
| title_sort | cancer outcomes and all cause mortality in adults allocated to metformin systematic review and collaborative meta analysis of randomised clinical trials |
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