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Metformin has been proposed as an effective adjunct to conventional anti-leukemia therapy, particularly to overcome drug resistance, but monotherapy is insufficient. This narrative review synthesizes evidence on metformin-based combination regimens and evaluates reported impacts on cellular metabolism, apoptosis, and clinical outcomes in AML.",{"@graph":69,"@context":126},[70,84,105],{"@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/therapeutic-potential-of-metformin-based-combination-therapy-in-acute-myeloid-leukemia-review-open-access/441178/",{"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/therapeutic-potential-of-metformin-based-combination-therapy-in-acute-myeloid-leukemia-review-open-access/441178.png","ImageObject",300,407,{"name":92,"@type":93},"Rowan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"Why is metformin considered for acute myeloid leukemia treatment?","Question",{"text":112,"@type":113},"Metformin may enhance the effectiveness of traditional anti-leukemia medications, especially against drug resistance, even though it is not effective as standalone therapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the literature evidence collected in this review?",{"text":117,"@type":113},"A narrative review searched PubMed, Google Scholar, Scopus, Embase, and Cochrane, identifying 103 relevant articles up to July 2024, with 32 included after exclusions.",{"name":119,"@type":110,"acceptedAnswer":120},"What biological effects do metformin-based combinations show in the included studies?",{"text":121,"@type":113},"Reported combinations reduce intracellular ATP, inhibit glycolysis, disrupt the cell cycle, diminish oxidative phosphorylation, increase anti-apoptotic protein expression, and increase cytotoxicity, leading to apoptosis and reduced AML growth.",{"name":123,"@type":110,"acceptedAnswer":124},"What overall conclusion does the review reach about combining drugs with metformin?",{"text":125,"@type":113},"Combining metformin with other therapies may strengthen synergistic effects and improve treatment outcomes for AML patients, including reducing AML burden and increasing overall survival.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},441178,1790829565,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":143,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":149,"preview_page_count":4},1099514067415,"https://ap-avatar.wpscdn.com/avatar/100002539d78ffe74a7?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779092875211072502","Shamahmood et al. Discover Oncology (2026) 17:12  \n[https://doi.org/10.1007/s12672-025-04205-4](https://doi.org/10.1007/s12672-025-04205-4)  \nDiscover Oncology  \nREVIEW Open Access  \nTherapeutic potential of metformin-based  \ncombination therapy in acute myeloid leukemia  \nMobina Nakhaei Shamahmood 1, Abolfazl Miri2, Mohammad JavadYousefi 1 and Fatemeh Mezginejad3*  \n*Correspondence:  \nFatemeh Mezginejad [mezginejadf@gmail.com](mezginejadf@gmail.com)[ ](mezginejadf@gmail.com)1Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran  \n2Student Research Committee, Zahedan University of Medical Sciences, Zahedan, Iran 3Department of Hematology, School of Allied Medicine, Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran  \nAbstract  \nBackground Acute myeloid leukemia (AML) is the most prevalent form of acute leukemia. Despite great efforts, the overall prognosis for patients with AML remains poor, and the mortality rate due to relapse is also considerable. Consequently, the disease poses treatment challenges. Several studies have indicated that metformin may serve as a beneficial adjunct to traditional anti-leukemia medications, especially enhancing their effectiveness against drug resistance; however, it is not effective when used as a standalone treatment. In this context, combination therapies are currently being explored as a promising treatment option.  \nMethods This study is a narrative review. A comprehensive literature search across multiple databases, including PubMed, Google Scholar, Scopus, Embase and Cochrane, yielded 103 relevant articles up to July 2024. From an initial total of 103 articles, we excluded unrelated and duplicate articles, as well as those for which the full text was unavailable and review articles. Ultimately, 32 articles were included in the study.  \nDuring the database search, we employed search terms such as AML, combination, and metformin to find relevant articles.  \nResults According to the results of the studies, the combination of metformin with gilteritinib, sorafenib, 6-benzylthionosine, venetoclax, diclofenac, diflunisal, and cytarabine reduces intracellular ATP levels, inhibits glycolysis, halts the cell cycle, diminishes oxidative phosphorylation, increases the expression of anti-apoptotic proteins and increases cytotoxicity. This combination also induces apoptosis, reduces cell growth, and ultimately leads to a significant decrease in the burden of AML and an increase in overall survival for these patients.  \nConclusions Therefore, combining these drugs with metformin may enhance the synergistic effect and improve the treatment of AML patients.  \nKeywords AML, Combination, Metformin  \n1 Introduction  \nAcute leukemia is a group of clonal and heterogeneous hematopoietic disorders characterized by the uncontrolled proliferation of immature blast cells. Among acute leukemias, acute lymphoblastic leukemia (ALL) is the most common form in children, whereas AML is the predominant acute leukemia in adults [1]. AML arises from genetic  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain p","cbCaidV2Zb8pOkJ7","https://ap.wps.com/l/cbCaidV2Zb8pOkJ7","pdf",1254264,15,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"Why is metformin considered for acute myeloid leukemia treatment?\",\"answer\":\"Metformin may enhance the effectiveness of traditional anti-leukemia medications, especially against drug resistance, even though it is not effective as standalone therapy.\"},{\"question\":\"How was the literature evidence collected in this review?\",\"answer\":\"A narrative review searched PubMed, Google Scholar, Scopus, Embase, and Cochrane, identifying 103 relevant articles up to July 2024, with 32 included after exclusions.\"},{\"question\":\"What biological effects do metformin-based combinations show in the included studies?\",\"answer\":\"Reported combinations reduce intracellular ATP, inhibit glycolysis, disrupt the cell cycle, diminish oxidative phosphorylation, increase anti-apoptotic protein expression, and increase cytotoxicity, leading to apoptosis and reduced AML growth.\"},{\"question\":\"What overall conclusion does the review reach about combining drugs with metformin?\",\"answer\":\"Combining metformin with other therapies may strengthen synergistic effects and improve treatment outcomes for AML patients, including reducing AML burden and increasing overall survival.\"}]","Therapeutic potential of metformin-based combination therapy in acute myeloid leukemia - review open access | PDF",1790695014,38]