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/usual...
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| Veröffentlicht in: | Diabetologia 2012-10, Vol.55 (10), p.2593-2603 |
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| creator | Stevens, R. J. Ali, R. 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. |
| 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. |
| doi_str_mv | 10.1007/s00125-012-2653-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1038228908</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1038228908</sourcerecordid><originalsourceid>FETCH-LOGICAL-c445t-f0bdd37a8575162ed4e5683c3f842719f14b635780e96e17740732d152806d223</originalsourceid><addsrcrecordid>eNp1kcuKFTEQhoMozpnRB3AjARFmE809aXfDwRsMuFFw1-Sk05Ih3RmT9Mh5FN_Wavt4QXBTBamv_lTVj9ATRl8wSs3LSinjikAgXCtBzD20Y1JwQiW399FuLRNm9eczdF7rDaVUKKkfojPOrVGsUzv0fe9mHwrOS_N5ChW7ecAuJeLdUgOecmkuxXbEccZuWFKrazV718KAW8ZTaGMuU5xf4XqsLUyuRY9LuIvh208tn1Nyh1zg_S6suCNudulYY8V5xAWYPMUKaj7FOXqXcCvRpfoIPRghhcenfIE-vXn9cf-OXH94-35_dU28lKqRkR6GQRhnFWykeRhkUNoKL0YruWHdyORBC2UsDZ0OzBhJjeADU9xSPXAuLtDlpntb8tcl1NbDOD7A1HPIS-0ZFRbu1VEL6LN_0Ju8FNhmo4zqhO2AYhvlS661hLG_LXFy5QhQv_rWb771EPrVt95Az9OT8nKYwvC745dRADw_Aa7CjUa4m4_1D6eFpNpo4PjGVSjNX0L5e8T__f4Dm3GxKg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1038759389</pqid></control><display><type>article</type><title>Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Stevens, R. J. ; Ali, R. ; 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.</creator><creatorcontrib>Stevens, R. J. ; Ali, R. ; 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.</creatorcontrib><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.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-012-2653-7</identifier><identifier>PMID: 22875195</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Cancer ; Clinical trials ; Collaboration ; Diabetes ; Diabetes Complications - complications ; Diabetes Mellitus - drug therapy ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinology ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Female ; Follow-Up Studies ; Glucose ; Human Physiology ; Humans ; Hypoglycemic Agents - therapeutic use ; Hypotheses ; Internal Medicine ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Meta-analysis ; Metabolic Diseases ; Metabolism ; Metformin - therapeutic use ; Middle Aged ; Mortality ; Neoplasms - epidemiology ; Neoplasms - mortality ; Observational studies ; Prevention ; Randomized Controlled Trials as Topic ; Risk Factors ; Survival Rate ; Systematic review</subject><ispartof>Diabetologia, 2012-10, Vol.55 (10), p.2593-2603</ispartof><rights>Springer-Verlag 2012</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-f0bdd37a8575162ed4e5683c3f842719f14b635780e96e17740732d152806d223</citedby><cites>FETCH-LOGICAL-c445t-f0bdd37a8575162ed4e5683c3f842719f14b635780e96e17740732d152806d223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-012-2653-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-012-2653-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26340676$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22875195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stevens, R. J.</creatorcontrib><creatorcontrib>Ali, R.</creatorcontrib><creatorcontrib>Bankhead, C. R.</creatorcontrib><creatorcontrib>Bethel, M. A.</creatorcontrib><creatorcontrib>Cairns, B. J.</creatorcontrib><creatorcontrib>Camisasca, R. P.</creatorcontrib><creatorcontrib>Crowe, F. L.</creatorcontrib><creatorcontrib>Farmer, A. J.</creatorcontrib><creatorcontrib>Harrison, S.</creatorcontrib><creatorcontrib>Hirst, J. A.</creatorcontrib><creatorcontrib>Home, P.</creatorcontrib><creatorcontrib>Kahn, S. E.</creatorcontrib><creatorcontrib>McLellan, J. H.</creatorcontrib><creatorcontrib>Perera, R.</creatorcontrib><creatorcontrib>Plüddemann, A.</creatorcontrib><creatorcontrib>Ramachandran, A.</creatorcontrib><creatorcontrib>Roberts, N. W.</creatorcontrib><creatorcontrib>Rose, P. W.</creatorcontrib><creatorcontrib>Schweizer, A.</creatorcontrib><creatorcontrib>Viberti, G.</creatorcontrib><creatorcontrib>Holman, R. R.</creatorcontrib><title>Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><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.</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Clinical trials</subject><subject>Collaboration</subject><subject>Diabetes</subject><subject>Diabetes Complications - complications</subject><subject>Diabetes Mellitus - drug therapy</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinology</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Glucose</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Hypotheses</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Meta-analysis</subject><subject>Metabolic Diseases</subject><subject>Metabolism</subject><subject>Metformin - therapeutic use</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Neoplasms - epidemiology</subject><subject>Neoplasms - mortality</subject><subject>Observational studies</subject><subject>Prevention</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Risk Factors</subject><subject>Survival Rate</subject><subject>Systematic review</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kcuKFTEQhoMozpnRB3AjARFmE809aXfDwRsMuFFw1-Sk05Ih3RmT9Mh5FN_Wavt4QXBTBamv_lTVj9ATRl8wSs3LSinjikAgXCtBzD20Y1JwQiW399FuLRNm9eczdF7rDaVUKKkfojPOrVGsUzv0fe9mHwrOS_N5ChW7ecAuJeLdUgOecmkuxXbEccZuWFKrazV718KAW8ZTaGMuU5xf4XqsLUyuRY9LuIvh208tn1Nyh1zg_S6suCNudulYY8V5xAWYPMUKaj7FOXqXcCvRpfoIPRghhcenfIE-vXn9cf-OXH94-35_dU28lKqRkR6GQRhnFWykeRhkUNoKL0YruWHdyORBC2UsDZ0OzBhJjeADU9xSPXAuLtDlpntb8tcl1NbDOD7A1HPIS-0ZFRbu1VEL6LN_0Ju8FNhmo4zqhO2AYhvlS661hLG_LXFy5QhQv_rWb771EPrVt95Az9OT8nKYwvC745dRADw_Aa7CjUa4m4_1D6eFpNpo4PjGVSjNX0L5e8T__f4Dm3GxKg</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>Stevens, R. J.</creator><creator>Ali, R.</creator><creator>Bankhead, C. R.</creator><creator>Bethel, M. A.</creator><creator>Cairns, B. J.</creator><creator>Camisasca, R. P.</creator><creator>Crowe, F. L.</creator><creator>Farmer, A. J.</creator><creator>Harrison, S.</creator><creator>Hirst, J. A.</creator><creator>Home, P.</creator><creator>Kahn, S. E.</creator><creator>McLellan, J. H.</creator><creator>Perera, R.</creator><creator>Plüddemann, A.</creator><creator>Ramachandran, A.</creator><creator>Roberts, N. W.</creator><creator>Rose, P. W.</creator><creator>Schweizer, A.</creator><creator>Viberti, G.</creator><creator>Holman, R. R.</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20121001</creationdate><title>Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials</title><author>Stevens, R. J. ; Ali, R. ; 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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-f0bdd37a8575162ed4e5683c3f842719f14b635780e96e17740732d152806d223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Clinical trials</topic><topic>Collaboration</topic><topic>Diabetes</topic><topic>Diabetes Complications - complications</topic><topic>Diabetes Mellitus - drug therapy</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinology</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Glucose</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Hypotheses</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Meta-analysis</topic><topic>Metabolic Diseases</topic><topic>Metabolism</topic><topic>Metformin - therapeutic use</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Neoplasms - epidemiology</topic><topic>Neoplasms - mortality</topic><topic>Observational studies</topic><topic>Prevention</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Risk Factors</topic><topic>Survival Rate</topic><topic>Systematic review</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stevens, R. J.</creatorcontrib><creatorcontrib>Ali, R.</creatorcontrib><creatorcontrib>Bankhead, C. R.</creatorcontrib><creatorcontrib>Bethel, M. A.</creatorcontrib><creatorcontrib>Cairns, B. J.</creatorcontrib><creatorcontrib>Camisasca, R. P.</creatorcontrib><creatorcontrib>Crowe, F. L.</creatorcontrib><creatorcontrib>Farmer, A. J.</creatorcontrib><creatorcontrib>Harrison, S.</creatorcontrib><creatorcontrib>Hirst, J. A.</creatorcontrib><creatorcontrib>Home, P.</creatorcontrib><creatorcontrib>Kahn, S. E.</creatorcontrib><creatorcontrib>McLellan, J. H.</creatorcontrib><creatorcontrib>Perera, R.</creatorcontrib><creatorcontrib>Plüddemann, A.</creatorcontrib><creatorcontrib>Ramachandran, A.</creatorcontrib><creatorcontrib>Roberts, N. W.</creatorcontrib><creatorcontrib>Rose, P. W.</creatorcontrib><creatorcontrib>Schweizer, A.</creatorcontrib><creatorcontrib>Viberti, G.</creatorcontrib><creatorcontrib>Holman, R. R.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stevens, R. J.</au><au>Ali, R.</au><au>Bankhead, C. R.</au><au>Bethel, M. A.</au><au>Cairns, B. J.</au><au>Camisasca, R. P.</au><au>Crowe, F. L.</au><au>Farmer, A. J.</au><au>Harrison, S.</au><au>Hirst, J. A.</au><au>Home, P.</au><au>Kahn, S. E.</au><au>McLellan, J. H.</au><au>Perera, R.</au><au>Plüddemann, A.</au><au>Ramachandran, A.</au><au>Roberts, N. W.</au><au>Rose, P. W.</au><au>Schweizer, A.</au><au>Viberti, G.</au><au>Holman, R. R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>55</volume><issue>10</issue><spage>2593</spage><epage>2603</epage><pages>2593-2603</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><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.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>22875195</pmid><doi>10.1007/s00125-012-2653-7</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0012-186X |
| ispartof | Diabetologia, 2012-10, Vol.55 (10), p.2593-2603 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1038228908 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Adult Aged Biological and medical sciences Cancer Clinical trials Collaboration Diabetes Diabetes Complications - complications Diabetes Mellitus - drug therapy Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinology Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Female Follow-Up Studies Glucose Human Physiology Humans Hypoglycemic Agents - therapeutic use Hypotheses Internal Medicine Male Medical sciences Medicine Medicine & Public Health Meta-analysis Metabolic Diseases Metabolism Metformin - therapeutic use Middle Aged Mortality Neoplasms - epidemiology Neoplasms - mortality Observational studies Prevention Randomized Controlled Trials as Topic Risk Factors Survival Rate Systematic review |
| title | Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-20T14%3A20%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cancer%20outcomes%20and%20all-cause%20mortality%20in%20adults%20allocated%20to%20metformin:%20systematic%20review%20and%20collaborative%20meta-analysis%20of%20randomised%20clinical%20trials&rft.jtitle=Diabetologia&rft.au=Stevens,%20R.%20J.&rft.date=2012-10-01&rft.volume=55&rft.issue=10&rft.spage=2593&rft.epage=2603&rft.pages=2593-2603&rft.issn=0012-186X&rft.eissn=1432-0428&rft_id=info:doi/10.1007/s00125-012-2653-7&rft_dat=%3Cproquest_cross%3E1038228908%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1038759389&rft_id=info:pmid/22875195&rfr_iscdi=true |