Expert consensus on metformin adjuvant therapy in malignant tumor patients with diabetes mellitus type 2 (2022 edition)

of Onco-endocrinology of Chinese Anti-Cancer Association Society

doi:10.19401/j.cnki.1007-3639.2022.11.011

您当前的位置：

首页 >

文章列表页 >

Expert consensus on metformin adjuvant therapy in malignant tumor patients with diabetes mellitus type 2 (2022 edition)

Guideline and Consensus | 更新时间：2025-12-31

- Expert consensus on metformin adjuvant therapy in malignant tumor patients with diabetes mellitus type 2 (2022 edition)
- China Oncology Vol. 32, Issue 11, Pages: 1121-1132(2022)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.11.011
  CLC： R730.5
- Received：19 August 2022，
  
  Revised：2022-10-12，
  
  Published：30 November 2022
- 稿件说明：
移动端阅览
of Onco-endocrinology of Chinese Anti-Cancer Association Society. Expert consensus on metformin adjuvant therapy in malignant tumor patients with diabetes mellitus type 2 (2022 edition)[J]. China Oncology, 2022, 32(11): 1121-1132.
DOI：

of Onco-endocrinology of Chinese Anti-Cancer Association Society. Expert consensus on metformin adjuvant therapy in malignant tumor patients with diabetes mellitus type 2 (2022 edition)[J]. China Oncology, 2022, 32(11): 1121-1132. DOI： 10.19401/j.cnki.1007-3639.2022.11.011.

摘要

恶性肿瘤是近年来慢性非传染性疾病死亡的主要原因，也是影响人类预期寿命的最重要原因，其治疗效果差，预后不良。二甲双胍为2型糖尿病首选的降糖药物，其抗肿瘤的作用得到越来越多同行的认可。然而，目前国内外缺乏独立的临床指南、共识及大型前瞻性临床试验。本共识旨在为二甲双胍在抗肿瘤方面的临床应用提供参考。对于大多数合并2型糖尿病的恶性肿瘤患者，推荐联合使用二甲双胍治疗，可以辅助抗肿瘤及增强化疗药物敏感性，降低多种恶性肿瘤的发病率、转移率，从而降低死亡率;对于少部分合并2型糖尿病的恶性肿瘤患者，不推荐也不反对使用二甲双胍，如雌激素受体（estrogen receptor，ER）阴性或三阴性乳腺癌;对于大部分不合并糖尿病的恶性肿瘤患者，不推荐使用二甲双胍，如肺癌、结直肠癌、前列腺癌等;而对于极少部分不合并糖尿病的恶性肿瘤患者，在充分知情同意的情况下，可使用二甲双胍。

Abstract

Malignant tumors are the leading causes of death from chronic non-communicable diseases and the most important factors influencing life expectancy in recent year

with poor treatment response and poor prognosis. Metformin

the preferred hypoglycemic drug for diabetes mellitus type 2

has been recognized by more and more peers for its anti-tumor effect. However

there is no independent clinical guideline

consensus and large prospective clinical trial at home and abroad. This expert guideline aimed to provide clinical practice reference for the application of metformin in anti-tumor treatment. This expert consensus recommends that metformin

used in combination for most malignancies with diabetes mellitus type 2

can assist in anti-tumor effect and enhance chemotherapeutic drug sensitivity

and reduce the morbidity and mortality of multiple malignancies. Metformin is not recommended or opposed for a small number of malignancies complicated with diabetes mellitus type 2

such as estrogen receptor (ER)-negative or triple-negative breast cancer. Metformin is not recommended for most malignant tumors without diabetes

such as lung cancer

colorectal cancer and prostate cancer. However

metformin can be used with informed consent in a very small number of malignancies without diabetes.

关键词

Keywords

references

SUNG H , FERLAY J , SIEGEL R L , et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 . DOI: 10.3322/caac.21660 http://doi.org/10.3322/caac.21660 https://onlinelibrary.wiley.com/doi/10.3322/caac.21660 https://onlinelibrary.wiley.com/doi/10.3322/caac.21660

刘师佺 , 周玉碧 , 李啟恩 , 等 . 基于德尔菲法的藏药“蒂达”药用资源和临床应用专家共识 [J ] . 中国药房 , 2021 , 32 ( 12 ): 1416 - 1420 .

LIU S Q , ZHOU Y B , LI Q E , et al. Expert consensus on the medicinal resources and clinical application of Tibetan medicine "dida" based on Delphi method [J ] . China Pharm , 2021 , 32 ( 12 ): 1416 - 1420 .

PODHORECKA M , IBANEZ B , DMOSZYŃSKA A . Metformin-its potential anti-cancer and anti-aging effects [J ] . Postepy Hig Med Dosw (Online) , 2017 , 71 ( 0 ): 170 - 175 .

ZHENG Z D , BIAN Y , ZHANG Y , et al. Metformin activates AMPK/SIRT1/NF-κB pathway and induces mitochondrial dysfunction to drive caspase3/GSDME-mediated cancer cell pyroptosis [J ] . Cell Cycle , 2020 , 19 ( 10 ): 1089 - 1104 . DOI: 10.1080/15384101.2020.1743911 http://doi.org/10.1080/15384101.2020.1743911

GWINN D M , SHACKELFORD D B , EGAN D F , et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint [J ] . Mol Cell , 2008 , 30 ( 2 ): 214 - 226 . DOI: 10.1016/j.molcel.2008.03.003 http://doi.org/10.1016/j.molcel.2008.03.003

YENMIŞ G , BEŞLI N , YAPRAK SARAÇ E , et al. Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism [J ] . Turk J Med Sci , 2021 , 51 ( 2 ): 826 - 834 . DOI: 10.3906/sag-1908-112 http://doi.org/10.3906/sag-1908-112

SUI X B , XU Y H , WANG X , et al. Metformin: a novel but controversial drug in cancer prevention and treatment [J ] . Mol Pharm , 2015 , 12 ( 11 ): 3783 - 3791 . DOI: 10.1021/acs.molpharmaceut.5b00577 http://doi.org/10.1021/acs.molpharmaceut.5b00577 https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.5b00577 https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.5b00577

LI M , HU X W , XU Y Q , et al. A possible mechanism of metformin in improving insulin resistance in diabetic rat models [J ] . Int J Endocrinol , 2019 , 2019 : 3248527 .

SUN R , ZHAI R , MA C , et al. Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway [J ] . Cancer Med , 2020 , 9 ( 3 ): 1141 - 1151 . DOI: 10.1002/cam4.2723 http://doi.org/10.1002/cam4.2723 https://onlinelibrary.wiley.com/doi/10.1002/cam4.2723 https://onlinelibrary.wiley.com/doi/10.1002/cam4.2723

LV Z Q , GUO Y J . Metformin and its benefits for various diseases [J ] . Front Endocrinol (Lausanne) , 2020 , 11 : 191 . DOI: 10.3389/fendo.2020.00191 http://doi.org/10.3389/fendo.2020.00191 https://www.frontiersin.org/article/10.3389/fendo.2020.00191/full https://www.frontiersin.org/article/10.3389/fendo.2020.00191/full

LIU Q L , TONG D L , LIU G L , et al. Metformin inhibits prostate cancer progression by targeting tumor-associated inflammatory infiltration [J ] . Clin Cancer Res , 2018 , 24 ( 22 ): 5622 - 5634 . DOI: 10.1158/1078-0432.CCR-18-0420 http://doi.org/10.1158/1078-0432.CCR-18-0420

KURELAC I , UMESH GANESH N , IORIO M , et al. The multifaceted effects of metformin on tumor microenvironment [J ] . Semin Cell Dev Biol , 2020 , 98 : 90 - 97 . DOI: S1084-9521(19)30077-1 http://doi.org/S1084-9521(19)30077-1

YE J , CHEN K , QI L , et al. Metformin suppresses hypoxia-induced migration via the HIF-1α/VEGF pathway in gallbladder cancer in vitro and in vivo [J ] . Oncol Rep , 2018 , 40 ( 6 ): 3501 - 3510 .

ORECCHIONI S , REGGIANI F , TALARICO G , et al. The biguanides metformin and phenformin inhibit angiogenesis, local and metastatic growth of breast cancer by targeting both neoplastic and microenvironment cells [J ] . Int J Cancer , 2015 , 136 ( 6 ): E534 -E544. DOI: 10.1002/ijc.29193 http://doi.org/10.1002/ijc.29193 https://onlinelibrary.wiley.com/doi/10.1002/ijc.29193 https://onlinelibrary.wiley.com/doi/10.1002/ijc.29193

ZHOU X K , CHEN J T , YI G , et al. Metformin suppresses hypoxia-induced stabilization of HIF-1α through reprogramming of oxygen metabolism in hepatocellular carcinoma [J ] . Oncotarget , 2016 , 7 ( 1 ): 873 - 884 . DOI: 10.18632/oncotarget.6418 http://doi.org/10.18632/oncotarget.6418

AHMED Z S O , GOLOVOY M , ABDULLAH Y , et al. Repurposing of metformin for cancer therapy: updated patent and literature review [J ] . Recent Pat Anticancer Drug Discov , 2021 , 16 ( 2 ): 161 - 186 . DOI: 10.2174/1574892816666210615163417 http://doi.org/10.2174/1574892816666210615163417

MALLIK R , CHOWDHURY T A . Metformin in cancer [J ] . Diabetes Res Clin Pract , 2018 , 143 : 409 - 419 . DOI: 10.1016/j.diabres.2018.05.023 http://doi.org/10.1016/j.diabres.2018.05.023 https://linkinghub.elsevier.com/retrieve/pii/S0168822717314109 https://linkinghub.elsevier.com/retrieve/pii/S0168822717314109

ROOS J F , QUDSI M , SAMARA A , et al. Metformin for lung cancer prevention and improved survival: a novel approach [J ] . Eur J Cancer Prev , 2019 , 28 ( 4 ): 311 - 315 . DOI: 10.1097/CEJ.0000000000000442 http://doi.org/10.1097/CEJ.0000000000000442

CEJUELA M , MARTIN-CASTILLO B , MENENDEZ J A , et al. Metformin and breast cancer: where are we now? [J ] . Int J Mol Sci , 2022 , 23 ( 5 ): 2705 . DOI: 10.3390/ijms23052705 http://doi.org/10.3390/ijms23052705 https://www.mdpi.com/1422-0067/23/5/2705 https://www.mdpi.com/1422-0067/23/5/2705

NG C A W , JIANG A A , TOH E M S , et al. Metformin and colorectal cancer: a systematic review, meta-analysis and meta-regression [J ] . Int J Colorectal Dis , 2020 , 35 ( 8 ): 1501 - 1512 . DOI: 10.1007/s00384-020-03676-x http://doi.org/10.1007/s00384-020-03676-x https://doi.org/10.1007/s00384-020-03676-x https://doi.org/10.1007/s00384-020-03676-x

ZAIDI S , GANDHI J , JOSHI G , et al. The anticancer potential of metformin on prostate cancer [J ] . Prostate Cancer Prostatic Dis , 2019 , 22 ( 3 ): 351 - 361 . DOI: 10.1038/s41391-018-0085-2 http://doi.org/10.1038/s41391-018-0085-2 https://doi.org/10.1038/s41391-018-0085-2 https://doi.org/10.1038/s41391-018-0085-2

COURTOIS S , LEHOURS P , BESSÈDE E . The therapeutic potential of metformin in gastric cancer [J ] . Gastric Cancer , 2019 , 22 ( 4 ): 653 - 662 . DOI: 10.1007/s10120-019-00952-w http://doi.org/10.1007/s10120-019-00952-w

MA S J , ZHENG Y X , ZHOU P C , et al. Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis [J ] . Oncotarget , 2016 , 7 ( 40 ): 66202 - 66211 . DOI: 10.18632/oncotarget.11033 http://doi.org/10.18632/oncotarget.11033 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.11033 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.11033

LENG W , JIANG J , CHEN B , et al. Metformin and malignant tumors: not over the hill [J ] . Diabetes Metab Syndr Obes , 2021 , 14 : 3673 - 3689 . DOI: 10.2147/DMSO.S326378 http://doi.org/10.2147/DMSO.S326378 https://www.dovepress.com/metformin-and-malignant-tumors-not-over-the-hill-peer-reviewed-fulltext-article-DMSO https://www.dovepress.com/metformin-and-malignant-tumors-not-over-the-hill-peer-reviewed-fulltext-article-DMSO

LI Y , HU L Y , XIA Q H , et al. The impact of metformin use on survival in kidney cancer patients with diabetes: a meta-analysis [J ] . Int Urol Nephrol , 2017 , 49 ( 6 ): 975 - 981 . DOI: 10.1007/s11255-017-1548-4 http://doi.org/10.1007/s11255-017-1548-4

LIU C Q , SUN J X , XU J Z , et al. Metformin use on incidence and oncologic outcomes of bladder cancer patients with T2DM: an updated meta-analysis [J ] . Front Pharmacol , 2022 , 13 : 865988 . DOI: 10.3389/fphar.2022.865988 http://doi.org/10.3389/fphar.2022.865988 https://www.frontiersin.org/articles/10.3389/fphar.2022.865988/full https://www.frontiersin.org/articles/10.3389/fphar.2022.865988/full

AHMED M F , KANAAN G , MOSTAFA J A . The role of metformin in ovarian cancer: does metformin increase survival in ovarian neoplasm? [J ] . Cureus , 2021 , 13 ( 2 ): e13100 .

BIONDANI G , PEYRON J F . Metformin, an anti-diabetic drug to target leukemia [J ] . Front Endocrinol (Lausanne) , 2018 , 9 : 446 . DOI: 10.3389/fendo.2018.00446 http://doi.org/10.3389/fendo.2018.00446 https://www.frontiersin.org/article/10.3389/fendo.2018.00446/full https://www.frontiersin.org/article/10.3389/fendo.2018.00446/full

JAUNE E , ROCCHI S . Metformin: focus on melanoma [J ] . Front Endocrinol (Lausanne) , 2018 , 9 : 472 . DOI: 10.3389/fendo.2018.00472 http://doi.org/10.3389/fendo.2018.00472 https://www.frontiersin.org/article/10.3389/fendo.2018.00472/full https://www.frontiersin.org/article/10.3389/fendo.2018.00472/full

MU N , XU T , GAO M , et al. Therapeutic effect of metformin in the treatment of endometrial cancer [J ] . Oncol Lett , 2020 , 20 ( 5 ): 156 . DOI: 10.3892/ol.2020.12017 http://doi.org/10.3892/ol.2020.12017

MAZUREK M , LITAK J , KAMIENIAK P , et al. Metformin as potential therapy for high-grade glioma [J ] . Cancers (Basel) , 2020 , 12 ( 1 ): E210 .

LIU B L , FAN Z Y , EDGERTON S M , et al. Potent anti-proliferative effects of metformin on trastuzumab-resistant breast cancer cells via inhibition of erbB2/IGF-1 receptor interactions [J ] . Cell Cycle , 2011 , 10 ( 17 ): 2959 - 2966 .

QU C , ZHANG W , ZHENG G , et al. Metformin reverses multidrug resistance and epithelial-mesenchymal transition (EMT) via activating AMP-activated protein kinase (AMPK) in human breast cancer cells [J ] . Mol Cell Biochem , 2014 , 386 ( 1/2 ): 63 - 71 . DOI: 10.1007/s11010-013-1845-x http://doi.org/10.1007/s11010-013-1845-x http://link.springer.com/10.1007/s11010-013-1845-x http://link.springer.com/10.1007/s11010-013-1845-x

RAO M Y , GAO C L , GUO M , et al. Effects of metformin treatment on radiotherapy efficacy in patients with cancer and diabetes: a systematic review and meta-analysis [J ] . Cancer Manag Res , 2018 , 10 : 4881 - 4890 . DOI: 10.2147/CMAR.S174535 http://doi.org/10.2147/CMAR.S174535

SAMSURI N A B , LEECH M , MARIGNOL L . Metformin and improved treatment outcomes in radiation therapy-a review [J ] . Cancer Treat Rev , 2017 , 55 : 150 - 162 . DOI: 10.1016/j.ctrv.2017.03.005 http://doi.org/10.1016/j.ctrv.2017.03.005 https://linkinghub.elsevier.com/retrieve/pii/S0305737217300427 https://linkinghub.elsevier.com/retrieve/pii/S0305737217300427

WRIGHT A D , CULL C A , MACLEOD K M , et al. Hypoglycemia in type 2 diabetic patients randomized to and maintained on monotherapy with diet, sulfonylurea, metformin, or insulin for 6 years from diagnosis: UKPDS73 [J ] . J Diabetes Complications , 2006 , 20 ( 6 ): 395 - 401 . DOI: 10.1016/j.jdiacomp.2005.08.010 http://doi.org/10.1016/j.jdiacomp.2005.08.010 https://linkinghub.elsevier.com/retrieve/pii/S1056872705001194 https://linkinghub.elsevier.com/retrieve/pii/S1056872705001194

MCCREIGHT L J , STAGE T B , CONNELLY P , et al. Pharmacokinetics of metformin in patients with gastrointestinal intolerance [J ] . Diabetes Obes Metab , 2018 , 20 ( 7 ): 1593 - 1601 . DOI: 10.1111/dom.13264 http://doi.org/10.1111/dom.13264

SOUKAS A A , HAO H B , WU L F . Metformin as anti-aging therapy: is it for everyone? [J ] . Trends Endocrinol Metab , 2019 , 30 ( 10 ): 745 - 755 . DOI: 10.1016/j.tem.2019.07.015 http://doi.org/10.1016/j.tem.2019.07.015 https://linkinghub.elsevier.com/retrieve/pii/S104327601930147X https://linkinghub.elsevier.com/retrieve/pii/S104327601930147X

LENG W L , PU D L , JIANG J , et al. Effect of metformin on breast density in overweight/obese premenopausal women [J ] . Diabetes Metab Syndr Obes , 2021 , 14 : 4423 - 4432 . DOI: 10.2147/DMSO.S330625 http://doi.org/10.2147/DMSO.S330625 https://www.dovepress.com/effect-of-metformin-on-breast-density-in-overweightobese-premenopausal-peer-reviewed-fulltext-article-DMSO https://www.dovepress.com/effect-of-metformin-on-breast-density-in-overweightobese-premenopausal-peer-reviewed-fulltext-article-DMSO

HIGURASHI T , HOSONO K , TAKAHASHI H , et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial [J ] . Lancet Oncol , 2016 , 17 ( 4 ): 475 - 483 . DOI: S1470-2045(15)00565-3 http://doi.org/S1470-2045(15)00565-3

TSENG C H . Metformin may reduce breast cancer risk in Taiwanese women with type 2 diabetes [J ] . Breast Cancer Res Treat , 2014 , 145 ( 3 ): 785 - 790 . DOI: 10.1007/s10549-014-2985-8 http://doi.org/10.1007/s10549-014-2985-8 http://link.springer.com/10.1007/s10549-014-2985-8 http://link.springer.com/10.1007/s10549-014-2985-8

CHEN L , CHUBAK J , BOUDREAU D M , et al. Diabetes treatments and risks of adverse breast cancer outcomes among early-stage breast cancer patients: a SEER-medicare analysis [J ] . Cancer Res , 2017 , 77 ( 21 ): 6033 - 6041 . DOI: 10.1158/0008-5472.CAN-17-0687 http://doi.org/10.1158/0008-5472.CAN-17-0687

TANG G H , SATKUNAM M , POND G R , et al. Association of metformin with breast cancer incidence and mortality in patients with type Ⅱ diabetes: a GRADE-assessed systematic review and meta-analysis [J ] . Cancer Epidemiol Biomark Prev , 2018 , 27 ( 6 ): 627 - 635 . DOI: 10.1158/1055-9965.EPI-17-0936 http://doi.org/10.1158/1055-9965.EPI-17-0936 https://aacrjournals.org/cebp/article/27/6/627/71589/Association-of-Metformin-with-Breast-Cancer https://aacrjournals.org/cebp/article/27/6/627/71589/Association-of-Metformin-with-Breast-Cancer

CHLEBOWSKI R T , MCTIERNAN A , WACTAWSKI-WENDE J , et al. Diabetes, metformin, and breast cancer in postmenopausal women [J ] . J Clin Oncol , 2012 , 30 ( 23 ): 2844 - 52 . DOI: 10.1200/JCO.2011.39.7505 http://doi.org/10.1200/JCO.2011.39.7505

PARK Y M M , BOOKWALTER D B , O’BRIEN K M , et al. A prospective study of type 2 diabetes, metformin use, and risk of breast cancer [J ] . Ann Oncol , 2021 , 32 ( 3 ): 351 - 359 . DOI: 10.1016/j.annonc.2020.12.008 http://doi.org/10.1016/j.annonc.2020.12.008

CHEN H J , COOK L S , TANG M C , et al. Relationship between diabetes and diabetes medications and risk of different molecular subtypes of breast cancer [J ] . Cancer Epidemiol Biomarkers Prev , 2019 , 28 ( 11 ): 1802 - 1808 . DOI: 10.1158/1055-9965.EPI-19-0291 http://doi.org/10.1158/1055-9965.EPI-19-0291 https://aacrjournals.org/cebp/article/28/11/1802/167466/Relationship-between-Diabetes-and-Diabetes https://aacrjournals.org/cebp/article/28/11/1802/167466/Relationship-between-Diabetes-and-Diabetes

BAYRAKTAR S , HERNADEZ-AYA L F , LEI X D , et al. Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer [J ] . Cancer , 2012 , 118 ( 5 ): 1202 - 1211 . DOI: 10.1002/cncr.26439 http://doi.org/10.1002/cncr.26439

DHILLON S S , GROMAN A , MEAGHER A , et al. Metformin and not diabetes influences the survival of resected early stage NSCLC patients [J ] . J Cancer Sci Ther , 2014 , 6 ( 7 ): 217 - 222 .

XU T B , LI D S , HE Y , et al. Prognostic value of metformin for non-small cell lung cancer patients with diabetes [J ] . World J Surg Oncol , 2018 , 16 ( 1 ): 60 . DOI: 10.1186/s12957-018-1362-1 http://doi.org/10.1186/s12957-018-1362-1

XU T , LIANG G , YANG L , et al. Prognosis of small cell lung cancer patients with diabetes treated with metformin [J ] . Clin Transl Oncol , 2015 , 17 ( 10 ): 819 - 824 . DOI: 10.1007/s12094-015-1311-1 http://doi.org/10.1007/s12094-015-1311-1

KONG F M , GAO F F , LIU H G , et al. Metformin use improves the survival of diabetic combined small-cell lung cancer patients [J ] . Tumour Biol , 2015 , 36 ( 10 ): 8101 - 8106 . DOI: 10.1007/s13277-015-3549-1 http://doi.org/10.1007/s13277-015-3549-1 http://link.springer.com/10.1007/s13277-015-3549-1 http://link.springer.com/10.1007/s13277-015-3549-1

KANG J H , JEONG S M , SHIN D W , et al. The associations of aspirin, statins, and metformin with lung cancer risk and related mortality: a time-dependent analysis of population-based nationally representative data [J ] . J Thorac Oncol , 2021 , 16 ( 1 ): 76 - 88 . DOI: 10.1016/j.jtho.2020.08.021 http://doi.org/10.1016/j.jtho.2020.08.021

ZENG S , GAN H X , XU J X , et al. Metformin improves survival in lung cancer patients with type 2 diabetes mellitus: a meta-analysis [J ] . Med Clin (Barc) , 2019 , 152 ( 8 ): 291 - 297 . DOI: 10.1016/j.medcli.2018.06.026 http://doi.org/10.1016/j.medcli.2018.06.026 https://linkinghub.elsevier.com/retrieve/pii/S0025775318304494 https://linkinghub.elsevier.com/retrieve/pii/S0025775318304494

BRANCHER S , STØER N C , WEIDERPASS E , et al. Metformin use and lung cancer survival: a population-based study in Norway [J ] . Br J Cancer , 2021 , 124 ( 5 ): 1018 - 1025 . DOI: 10.1038/s41416-020-01186-9 http://doi.org/10.1038/s41416-020-01186-9 https://doi.org/10.1038/s41416-020-01186-9 https://doi.org/10.1038/s41416-020-01186-9

BRADLEY M C , FERRARA A , ACHACOSO N , et al. A cohort study of metformin and colorectal cancer risk among patients with diabetes mellitus [J ] . Cancer Epidemiol Biomarkers Prev , 2018 , 27 ( 5 ): 525 - 530 . DOI: 10.1158/1055-9965.EPI-17-0424 http://doi.org/10.1158/1055-9965.EPI-17-0424 https://aacrjournals.org/cebp/article/27/5/525/71475/A-Cohort-Study-of-Metformin-and-Colorectal-Cancer https://aacrjournals.org/cebp/article/27/5/525/71475/A-Cohort-Study-of-Metformin-and-Colorectal-Cancer

FERNANDES J M , JANDREY E H F , KOYAMA F C , et al. Metformin as an alternative radiosensitizing agent to 5-fluorouracil during neoadjuvant treatment for rectal cancer [J ] . Dis Colon Rectum , 2020 , 63 ( 7 ): 918 - 926 . DOI: 10.1097/DCR.0000000000001626 http://doi.org/10.1097/DCR.0000000000001626

XIE J Y , XIA L P , XIANG W , et al. Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1 [J ] . Proc Natl Acad Sci USA , 2020 , 117 ( 23 ): 13012 - 13022 . DOI: 10.1073/pnas.1918845117 http://doi.org/10.1073/pnas.1918845117 https://pnas.org/doi/full/10.1073/pnas.1918845117 https://pnas.org/doi/full/10.1073/pnas.1918845117

FRANSGAARD T , THYGESEN L C , GÖGENUR I . Association between metformin use after surgery for colorectal cancer and oncological outcomes: a nationwide register-based study [J ] . Int J Cancer , 2018 , 143 ( 1 ): 63 - 72 . DOI: 10.1002/ijc.31305 http://doi.org/10.1002/ijc.31305

MC MENAMIN Ú C , MURRAY L J , HUGHES C M , et al. Metformin use and survival after colorectal cancer: a population-based cohort study [J ] . Int J Cancer , 2016 , 138 ( 2 ): 369 - 379 . DOI: 10.1002/ijc.29720 http://doi.org/10.1002/ijc.29720

KASPER J S , GIOVANNUCCI E . A meta-analysis of diabetes mellitus and the risk of prostate cancer [J ] . Cancer Epidemiol Biomarkers Prev , 2006 , 15 ( 11 ): 2056 - 2062 . DOI: 10.1158/1055-9965.EPI-06-0410 http://doi.org/10.1158/1055-9965.EPI-06-0410 https://aacrjournals.org/cebp/article/15/11/2056/275040/A-Meta-analysis-of-Diabetes-Mellitus-and-the-Risk https://aacrjournals.org/cebp/article/15/11/2056/275040/A-Meta-analysis-of-Diabetes-Mellitus-and-the-Risk

HANKINSON S J , FAM M , PATEL N N . A review for clinicians: prostate cancer and the antineoplastic properties of metformin [J ] . Urol Oncol , 2017 , 35 ( 1 ): 21 - 29 . DOI: S1078-1439(16)30316-7 http://doi.org/S1078-1439(16)30316-7

LEE M J , JAYALATH V H , XU W , et al. Association between metformin medication, genetic variation and prostate cancer risk [J ] . Prostate Cancer Prostatic Dis , 2021 , 24 ( 1 ): 96 - 105 . DOI: 10.1038/s41391-020-0238-y http://doi.org/10.1038/s41391-020-0238-y https://doi.org/10.1038/s41391-020-0238-y https://doi.org/10.1038/s41391-020-0238-y

MARGEL D , URBACH D R , LIPSCOMBE L L , et al. Metformin use and all-cause and prostate cancer-specific mortality among men with diabetes [J ] . J Clin Oncol , 2013 , 31 ( 25 ): 3069 - 3075 . DOI: 10.1200/JCO.2012.46.7043 http://doi.org/10.1200/JCO.2012.46.7043

TSENG C H . Metformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitus [J ] . Eur J Cancer , 2014 , 50 ( 16 ): 2831 - 2837 . DOI: 10.1016/j.ejca.2014.08.007 http://doi.org/10.1016/j.ejca.2014.08.007 https://linkinghub.elsevier.com/retrieve/pii/S0959804914008867 https://linkinghub.elsevier.com/retrieve/pii/S0959804914008867

YANG B , DAMODARAN S , KHEMEES T A , et al. Synthetic lethal metabolic targeting of androgen-deprived prostate cancer cells with metformin [J ] . Mol Cancer Ther , 2020 , 19 ( 11 ): 2278 - 2287 . DOI: 10.1158/1535-7163.MCT-19-1141 http://doi.org/10.1158/1535-7163.MCT-19-1141

ZHOU X L , XUE W H , DING X F , et al. Association between metformin and the risk of gastric cancer in patients with type 2 diabetes mellitus: a meta-analysis of cohort studies [J ] . Oncotarget , 2017 , 8 ( 33 ): 55622 - 55631 . DOI: 10.18632/oncotarget.16973 http://doi.org/10.18632/oncotarget.16973 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.16973 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.16973

TSENG C H . Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus [J ] . Aging (Albany NY) , 2016 , 8 ( 8 ): 1636 - 1649 .

CHEUNG K S , CHAN E W , WONG A Y S , et al. Metformin use and gastric cancer risk in diabetic patients after helicobacter pylori eradication [J ] . J Natl Cancer Inst , 2019 , 111 ( 5 ): 484 - 489 . DOI: 10.1093/jnci/djy144 http://doi.org/10.1093/jnci/djy144

LEE C K , JUNG M , JUNG I , et al. Cumulative metformin use and its impact on survival in gastric cancer patients after gastrectomy [J ] . Ann Surg , 2016 , 263 ( 1 ): 96 - 102 . DOI: 10.1097/SLA.0000000000001086 http://doi.org/10.1097/SLA.0000000000001086 https://journals.lww.com/00000658-201601000-00016 https://journals.lww.com/00000658-201601000-00016

KIM J , HYUN H J , CHOI E A , et al. Metformin use reduced the risk of stomach cancer in diabetic patients in Korea: an analysis of Korean NHIS-HEALS database [J ] . Gastric Cancer , 2020 , 23 ( 6 ): 1075 - 1083 . DOI: 10.1007/s10120-020-01085-1 http://doi.org/10.1007/s10120-020-01085-1 https://doi.org/10.1007/s10120-020-01085-1 https://doi.org/10.1007/s10120-020-01085-1

DONADON V , BALBI M , GHERSETTI M , et al. Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease [J ] . World J Gastroenterol , 2009 , 15 ( 20 ): 2506 - 2511 . DOI: 10.3748/wjg.15.2506 http://doi.org/10.3748/wjg.15.2506 http://www.wjgnet.com/1007-9327/full/v15/i20/2506.htm http://www.wjgnet.com/1007-9327/full/v15/i20/2506.htm

DONADON V , BALBI M , MAS M D , et al. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease [J ] . Liver Int , 2010 , 30 ( 5 ): 750 - 758 . DOI: 10.1111/j.1478-3231.2010.02223.x http://doi.org/10.1111/j.1478-3231.2010.02223.x

LEE M S , HSU C C , WAHLQVIST M L , et al. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800 000 individuals [J ] . BMC Cancer , 2011 , 11 : 20 . DOI: 10.1186/1471-2407-11-20 http://doi.org/10.1186/1471-2407-11-20 http://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-11-20 http://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-11-20

SHANKARAIAH R C , CALLEGARI E , GUERRIERO P , et al. Metformin prevents liver tumourigenesis by attenuating fibrosis in a transgenic mouse model of hepatocellular carcinoma [J ] . Oncogene , 2019 , 38 ( 45 ): 7035 - 7045 . DOI: 10.1038/s41388-019-0942-z http://doi.org/10.1038/s41388-019-0942-z

FERLAY J , COLOMBET M , SOERJOMATARAM I , et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods [J ] . Int J Cancer , 2019 , 144 ( 8 ): 1941 - 1953 . DOI: 10.1002/ijc.31937 http://doi.org/10.1002/ijc.31937

BOKHMAN J V . Two pathogenetic types of endometrial carcinoma [J ] . Gynecol Oncol , 1983 , 15 ( 1 ): 10 - 17 .

LEE T Y , MARTINEZ-OUTSCHOORN U E , SCHILDER R J , et al. Metformin as a therapeutic target in endometrial cancers [J ] . Front Oncol , 2018 , 8 : 341 . DOI: 10.3389/fonc.2018.00341 http://doi.org/10.3389/fonc.2018.00341

WU J W , BOUDREAU D M , PARK Y , et al. Commonly used diabetes and cardiovascular medications and cancer recurrence and cancer-specific mortality: a review of the literature [J ] . Expert Opin Drug Saf , 2014 , 13 ( 8 ): 1071 - 1099 . DOI: 10.1517/14740338.2014.926887 http://doi.org/10.1517/14740338.2014.926887

ZHANG Z J , LI S . The prognostic value of metformin for cancer patients with concurrent diabetes: a systematic review and meta-analysis [J ] . Diabetes Obes Metab , 2014 , 16 ( 8 ): 707 - 710 . DOI: 10.1111/dom.12267 http://doi.org/10.1111/dom.12267

KO E M , WALTER P , JACKSON A , et al. Metformin is associated with improved survival in endometrial cancer [J ] . Gynecol Oncol , 2014 , 132 ( 2 ): 438 - 442 . DOI: 10.1016/j.ygyno.2013.11.021 http://doi.org/10.1016/j.ygyno.2013.11.021

HANNA R K , ZHOU C X , MALLOY K M , et al. Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway [J ] . Gynecol Oncol , 2012 , 125 ( 2 ): 458 - 469 . DOI: 10.1016/j.ygyno.2012.01.009 http://doi.org/10.1016/j.ygyno.2012.01.009

ARIMA R , MARTTILA M , HAUTAKOSKI A , et al. Antidiabetic medication, statins and the risk and prognosis of non-endometrioid endometrial cancer in women with type 2 diabetes [J ] . Anticancer Res , 2018 , 38 ( 7 ): 4169 - 4178 . DOI: 10.21873/anticanres.12710 http://doi.org/10.21873/anticanres.12710

URPILAINEN E , ARIMA R , KARIHTALA P , et al. Metformin associates with aggressive features of endometrial cancer in women with type 2 diabetes [J ] . Anticancer Res , 2021 , 41 ( 2 ): 821 - 828 . DOI: 10.21873/anticanres.14834 http://doi.org/10.21873/anticanres.14834

MEIRELES C G , PEREIRA S A , VALADARES L P , et al. Effects of metformin on endometrial cancer: Systematic review and meta-analysis [J ] . Gynecol Oncol , 2017 , 147 ( 1 ): 167 - 180 . DOI: S0090-8258(17)31136-8 http://doi.org/S0090-8258(17)31136-8

CHAE-KIM J , GARG G , GAVRILOVA-JORDAN L , et al. Outcomes of women treated with progestin and metformin for atypical endometrial hyperplasia and early endometrial cancer: a systematic review and meta-analysis [J ] . Int J Gynecol Cancer , 2021 , 31 ( 12 ): 1499 - 1505 . DOI: 10.1136/ijgc-2021-002699 http://doi.org/10.1136/ijgc-2021-002699

YANG B Y , GULINAZI Y , DU Y , et al. Metformin plus megestrol acetate compared with megestrol acetate alone as fertility-sparing treatment in patients with atypical endometrial hyperplasia and well-differentiated endometrial cancer: a randomised controlled trial [J ] . BJOG , 2020 , 127 ( 7 ): 848 - 857 . DOI: 10.1111/1471-0528.16108 http://doi.org/10.1111/1471-0528.16108 https://onlinelibrary.wiley.com/doi/10.1111/1471-0528.16108 https://onlinelibrary.wiley.com/doi/10.1111/1471-0528.16108

GONG H , CHEN Y , ZHOU D C . Prognostic significance of metformin treatment in endometrial cancer: a meta-analysis [J ] . Pharmazie , 2020 , 75 ( 8 ): 401 - 406 . DOI: 10.1691/ph.2020.0346 http://doi.org/10.1691/ph.2020.0346

TSENG C H . Metformin and biliary tract cancer in patients with type 2 diabetes [J ] . Front Oncol , 2020 , 10 : 587666 . DOI: 10.3389/fonc.2020.587666 http://doi.org/10.3389/fonc.2020.587666 https://www.frontiersin.org/articles/10.3389/fonc.2020.587666/full https://www.frontiersin.org/articles/10.3389/fonc.2020.587666/full

BOLEN S , FELDMAN L , VASSY J , et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus [J ] . Ann Intern Med , 2007 , 147 ( 6 ): 386 - 399 .

FUJITA Y , INAGAKI N . Metformin: new preparations and nonglycemic benefits [J ] . Curr Diab Rep , 2017 , 17 ( 1 ): 5 . DOI: 10.1007/s11892-017-0829-8 http://doi.org/10.1007/s11892-017-0829-8 http://link.springer.com/10.1007/s11892-017-0829-8 http://link.springer.com/10.1007/s11892-017-0829-8

KHURANA R , MALIK I S . Metformin: safety in cardiac patients [J ] . Postgrad Med J , 2010 , 86 ( 1016 ): 371 - 373 . DOI: 10.1136/hrt.2009.173773 http://doi.org/10.1136/hrt.2009.173773

NATHAN D M , BUSE J B , DAVIDSON M B , et al. Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the study of diabetes [J ] . Diabetologia , 2009 , 52 ( 1 ): 17 - 30 . DOI: 10.1007/s00125-008-1157-y http://doi.org/10.1007/s00125-008-1157-y

TEALE K F , DEVINE A , STEWART H , et al. The management of metformin overdose [J ] . Anaesthesia , 1998 , 53 ( 7 ): 698 - 701 .

SELIGER C , MEYER A L , RENNER K , et al. Metformin inhibits proliferation and migration of glioblastoma cells independently of TGF-β2 [J ] . Cell Cycle , 2016 , 15 ( 13 ): 1755 - 1766 . DOI: 10.1080/15384101.2016.1186316 http://doi.org/10.1080/15384101.2016.1186316

YU Z Y , ZHAO G , XIE G F , et al. Metformin and temozolomide act synergistically to inhibit growth of glioma cells and glioma stem cells in vitro and in vivo [J ] . Oncotarget , 2015 , 6 ( 32 ): 32930 - 32943 . DOI: 10.18632/oncotarget.5405 http://doi.org/10.18632/oncotarget.5405 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.5405 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.5405

SELIGER C , RENNER K , KREUTZ M , et al. p17.39 turn old into new: metformin as antineoplastic agent in glioblastoma [J ] . Neuro-Oncology , 2014 , 16 ( suppl 2 ): ii96 .

LIN H C , KACHINGWE B H , LIN H L , et al. Effects of metformin dose on cancer risk reduction in patients with type 2 diabetes mellitus: a 6-year follow-up study [J ] . Pharmacotherapy , 2014 , 34 ( 1 ): 36 - 45 . DOI: 10.1002/phar.1334 http://doi.org/10.1002/phar.1334 https://onlinelibrary.wiley.com/doi/10.1002/phar.1334 https://onlinelibrary.wiley.com/doi/10.1002/phar.1334

Metformin: a practical guide to optimising outcomes round-table discussion held in Edinburgh [J ] . Br J Diabetes Vasc Dis , 2008 , 8 : 153 - 155 . DOI: 10.1177/14746514080080030801 http://doi.org/10.1177/14746514080080030801 http://journals.sagepub.com/doi/10.1177/14746514080080030801 http://journals.sagepub.com/doi/10.1177/14746514080080030801

HIRSCH H A , ILIOPOULOS D , TSICHLIS P N , et al. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission [J ] . Cancer Res , 2009 , 69 ( 19 ): 7507 - 7511 . DOI: 10.1158/0008-5472.CAN-09-2994 http://doi.org/10.1158/0008-5472.CAN-09-2994

ILIOPOULOS D , HIRSCH H A , STRUHL K . Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types [J ] . Cancer Res , 2011 , 71 ( 9 ): 3196 - 3201 . DOI: 10.1158/0008-5472.CAN-10-3471 http://doi.org/10.1158/0008-5472.CAN-10-3471

LIU H Y , SCHOLZ C , ZANG C B , et al. Metformin and the mTOR inhibitor everolimus (RAD001) sensitize breast cancer cells to the cytotoxic effect of chemotherapeutic drugs in vitro [J ] . Anticancer Res , 2012 , 32 ( 5 ): 1627 - 1637 .

CHATTERJEE S , THAKER N , DE A . Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells [J ] . Breast Cancer (Dove Med Press) , 2015 , 7 : 251 - 265 .

PENG M , DARKO K O , TAO T , et al. Combination of metformin with chemotherapeutic drugs via different molecular mechanisms [J ] . Cancer Treat Rev , 2017 , 54 : 24 - 33 . DOI: S0305-7372(17)30005-1 http://doi.org/S0305-7372(17)30005-1

BRAGAGNOLI A C , ARAUJO R L C , FERRAZ M W , et al. Metformin plus lrinotecan in patients with refractory colorectal cancer: a phase 2 clinical trial [J ] . Br J Cancer , 2021 , 124 ( 6 ): 1072 - 1078 . DOI: 10.1038/s41416-020-01208-6 http://doi.org/10.1038/s41416-020-01208-6 https://doi.org/10.1038/s41416-020-01208-6 https://doi.org/10.1038/s41416-020-01208-6

ROSHAN M H K , SHING Y K , PACE N P . Metformin as an adjuvant in breast cancer treatment [J ] . SAGE Open Med , 2019 , 7 : 2050312119865114 .

STOROZHUK Y , HOPMANS SN , SANLI T , et al. Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK [J ] . Br J Cancer , 2013 , 108 ( 10 ): 2021 - 2032 . DOI: 10.1038/bjc.2013.187 http://doi.org/10.1038/bjc.2013.187 https://doi.org/10.1038/bjc.2013.187 https://doi.org/10.1038/bjc.2013.187

GULATI S , DESAI J , PALACKDHARRY S M , et al. Phase 1 dose-finding study of metformin in combination with concurrent cisplatin and radiotherapy in patients with locally advanced head and neck squamous cell cancer [J ] . Cancer , 2020 , 126 ( 2 ): 354 - 362 . DOI: 10.1002/cncr.32539 http://doi.org/10.1002/cncr.32539

Views

1176

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Expert consensus on perioperative comprehensive treatment for high risk prostate cancer (2023 edition)

MDT consensus on immunotherapy for locally advanced head and neck squamous cell carcinoma (2025 edition)

Expert consensus on diagnosis and treatment of hematologic malignancies with solid tumors (2025 version)

Expert consensus on the combination of anti-EGFR monoclonal antibodies and immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma (2025 edition)

Progress and future prospects in local and systemic treatment of early breast cancer

Related Author

of Male Reproductive System Oncology Society

Anti-Cancer Association China

Chenping ZHANG

Chaosu HU

Ye GUO

Multiple Primary and Unknown Primary Tumors Special Committee of China Anti-Cancer Association

Shanghai Anti Cancer Association Multiple Primary and Unknown Primary Tumor Special Committee

Lymphocytic Disease Group, Hematology Branch, Chinese Medical Association

Related Institution

Committee of Head and Neck Cancer, Chinese Society of Clinical Oncology

Department of Breast Surgery, Fudan University Shanghai Cancer Center/Fudan University Breast Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University

Gynecologic Oncology Genetic Counseling Collaboration Group, Chinese Tertiary Obstetrics and Gynecology Hospital/Materning and Child Healthcare Hospital Alliance; Integrated Chinese and Western Endometrial Cancer Professional Committee, Chinese Anti-Cancer Association

Department of Clinical Laboratory, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University

Department of Clinical Laboratory, Shuguang Hospital of Shanghai University of Traditional Chinese Medicine

AI问答

⁰