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This comprehensive systematic review and meta-analysis synthesizes outcomes across multiple cancer types, accounting for metformin’s effects on cancer incidence, death, and survival. Literature was searched through October 15, 2024 in Medline, Embase, and Web of Science, with bias assessed using ROBINS-I and RoB 2 and evidence graded by GRADE. Among 65 studies, metformin intake reduced overall cancer risk and significantly lowered breast and colorectal cancer risks, but causal inference from observational designs is limited, warranting large RCTs.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/metformin-a-dual-role-player-in-cancer-treatment-and-prevention-a-comprehensive-systematic-review-and-meta-analysis/369614/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/metformin-a-dual-role-player-in-cancer-treatment-and-prevention-a-comprehensive-systematic-review-and-meta-analysis/369614.png","ImageObject",300,407,{"name":92,"@type":93},"Aditya","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main purpose of this systematic review and meta-analysis?","Question",{"text":113,"@type":114},"To synthesize evidence on the relationship between metformin use and cancer incidence, mortality, and survival, while assessing evidence quality and sources of heterogeneity and limitations.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was the literature search conducted?",{"text":118,"@type":114},"The review searched Medline (via PubMed), Embase, and Web of Science from the earliest possible date up to October 2024, with the final search date set to 15 October 2024.",{"name":120,"@type":111,"acceptedAnswer":121},"What overall effect of metformin on cancer risk was reported?",{"text":122,"@type":114},"Across 65 included studies, metformin intake was associated with a lower overall cancer risk (RR 0.72; 95% CI: 0.64–0.81), with significant reductions noted for breast and colorectal cancers.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},369614,1790217226,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},962085564549,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Systematic Review  \nMetformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis  \nImran Rangraze 1, *, Adil Farooq Wali 2, Mohamed El-Tanani 2, Mohamed Anas Patni 3,  \nSyed Arman Rabbani 2, Rasha Babiker 4, Shakta Mani Satyam 5, Yahia El-Tanani 6 and Manfredi Rizzo 1,7  \nAcademic Editor: Robert Ancuceanu  \nReceived: 9 April 2025  \nRevised: 28 April 2025  \nAccepted: 16 May 2025  \nPublished: 30 May 2025  \nCitation: Rangraze, I.; Wali, A.F.; El-Tanani, M.; Patni, M.A.; Rabbani, S.A.; Babiker, R.; Satyam, S.M.;  \nEl-Tanani, Y.; Rizzo, M. Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis. Medicina 2025, 61, 1021. [https://](https://)[ ](https://)[doi.org/10.3390/medicina61061021](doi.org/10.3390/medicina61061021)  \n[Copyright:](Copyright:) © 2025 by the authors. Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Internal Medicine Department, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates  \n2 College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates  \n3 Community Medicine, College of Medicine, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates  \n4 Physiology, College of Medicine, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates  \n5 Pharmacology, College of Medicine, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates  \n6 Royal Cornwall Hospital Trust, NHS, Truro TR1 3LJ, UK  \n7 Department of Endocrinology, School of Medicine, University of Palermo, 90133 Palermo, Italy  \n* Correspondence: [imranrashid@rakmhsu.ac.ae](imranrashid@rakmhsu.ac.ae)  \nAbstract: Background and Objectives: Metformin is said to reduce the incidences and deaths resulting from cancer in patients suffering from type 2 diabetes mellitus, but the results have been inconsistent. Perform a systematic review and meta-analysis concentrating on the different outcomes of several cancers while taking into account the impact of metforminuse. Materials and Methods: As of 15 October 2024, the literature for Medline, Embase, and Web of Science was systematically searched. ROBINS-I and the RoB 2 tool were used for assessing the risk of bias in observational studies and randomized controlled trials (RCTs), respectively. The strength of the evidence with respect to the GRADE criteria was checked. Random effects meta-analyses were conducted alongside sensitivity analyses, subgroup analyses, and meta-regressions. By utilizing funnel plots as well as Egger’s test and trim-and-fill analysis, publication bias was evaluated. Results: In total, 65 studies were included in the final analyses: Metformin intake was linked to a lower risk of cancer (RR 0.72; 95% CI: 0.64–0.81, I2 = 45%) . Significant reductions were observed in breast cancer (RR 0.68; 95% CI: 0.55–0.83) and colorectal cancers (RR 0.62; 95% CI: 0.51–0.76) . Evidence certainty fluctuated from moderate to low, though analyses confirmed the results. Plofs funded the publication bias, but adjustment in trim-and-fill did not change the outcome significantly. Conclusions: Metformin intake seems to lower the chances of developing several types of cancers, especially breast and colorectal cancers, but the observational designs hinder determining the causal factors for observational studies. There is a need for large RCTs.  \nKeywords: metformin;","cbCaibnTnsAxjn43","https://ap.wps.com/l/cbCaibnTnsAxjn43","pdf",1367404,29,"English","# Introduction\n## Materials and Methods\n### Search Strategy","[{\"question\":\"What is the main purpose of this systematic review and meta-analysis?\",\"answer\":\"To synthesize evidence on the relationship between metformin use and cancer incidence, mortality, and survival, while assessing evidence quality and sources of heterogeneity and limitations.\"},{\"question\":\"How was the literature search conducted?\",\"answer\":\"The review searched Medline (via PubMed), Embase, and Web of Science from the earliest possible date up to October 2024, with the final search date set to 15 October 2024.\"},{\"question\":\"What overall effect of metformin on cancer risk was reported?\",\"answer\":\"Across 65 included studies, metformin intake was associated with a lower overall cancer risk (RR 0.72; 95% CI: 0.64–0.81), with significant reductions noted for breast and colorectal cancers.\"}]","Metformin: A Dual-Role Player in Cancer Treatment and Prevention - A Comprehensive Systematic Review and Meta-Analysis | PDF",1790183681,73]