Cancer; Type 2 diabetes; Metformin; Mortality; Prevention
Abstract :
[en] Numerous epidemiological cohort and case-control studies showed that type 2 diabetes is a risk factor for cancer and that metformin therapy is associated with a significant reduction in the incidence of cancer and cancer-related death when compared to other glucose-lowering agents. Such beneficial effect is observed whatever the type of cancer, but seems to be more prominent in case of gastrointestinal and breast cancers. In general, the protective effect was more evident in observational cohort studies (however, more exposed to bias due to confounding factors) than in case-control studies. However, the results of the rather rare controlled clinical trials available are not conclusive, but none of them was performed with the objective to specifically assess cancer risk. Several meta-analyses recently confirmed that metformin therapy reduces the incidence of cancers (including colorectal cancer, hepatocarcinoma, breast cancer) and cancer-related mortality. Metformin may exert its anti-cancer activity by a direct effect (insulin) and an indirect effect (AMPK and mTOR). Considering all promising clinical information in patients with type 2 diabetes, further clinical trials are currently ongoing with the aim of assessing the role of metformin in oncology, especially as adjuvant in breast cancer therapy. [fr] Résumé : De nombreuses études épidémiologiques observationnelles
récentes, de cohortes et cas-témoins, révèlent que le
diabète de type 2 est un facteur de risque de cancer et qu’un
traitement par metformine est associé à une réduction significative
de l’incidence de néoplasies et de la mortalité y afférente
par comparaison à d’autres traitements anti-hyperglycémiants.
Cette protection concerne quasi tous les cancers, mais semble
surtout importante dans les cancers digestifs et les cancers du
sein. D’une façon générale, l’effet protecteur de la metformine
s’avère plus marqué dans les études de cohortes (par ailleurs,
davantage exposées à des biais) que dans les études cas-témoins.
Par contre, les résultats des rares essais cliniques contrôlés disponibles,
analysés a posteriori, ne sont guère concluants, mais
aucun n’avait été planifié à cet effet. Plusieurs méta-analyses
récentes ont confirmé qu’un traitement par metformine réduit
l’incidence de cancers de tout type (y compris cancer colo-rectal,
hépatocarcinome, cancer du sein) et la mortalité liée à ces
cancers. La metformine pourrait exercer son action anti-cancéreuse
par un effet indirect (insuline) et par un effet direct
(AMPK et mTOR). Au vu de l’ensemble des éléments cliniques
prometteurs disponibles chez les patients diabétiques de type
2, des études cliniques avec la metformine sont actuellement en
cours en oncologie, notamment comme adjuvant dans le traitement
du cancer du sein.
Mots-clés : Cancer - Diabète de type 2 - Metformine -
Mortalité - Prevention
Giovannucci E, Harlan DM, Archer MC, et al.- Diabetes and cancer : a consensus report. Diabetes Care, 2010, 33, 1674-1685.
Scheen AJ, Beck E, De Flines J, et al.- Obésité, insulinorésistance et diabéte de type 2 : facteurs de risque du cancer du sein. Rev Med Liege, 2011, 66, 238-244.
Godsland IF.- Insulin resistance and hyperinsulinaemia in the development and progression of cancer. Clin Sci, 2010, 118, 315-332.
Wysocki PJ, Wierusz-Wysocka B.- Obesity, hyperinsulinemia and breast cancer: novel targets and a novel role for metformin. Exp Rev Mol Diagn, 2010, 10, 509-519.
Cohen DH, LeRoith D.- Obesity, type 2 diabetes, and cancer: the insulin and IGF connection. Endocr Relat Cancer, 2012, 19, 27-45.
Smith U, Gale EA.- Does diabetes therapy influence the risk of cancer? Diabetologia, 2009, 52, 1699-1708.
Currie CJ, Poole CD, Gale EA.- The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia, 2009, 52, 1766-1777.
Onitilo AA, Engel JM, Glurich I, et al.- Diabetes and cancer II: role of diabetes medications and influence of shared risk factors. Cancer Causes Control, 2012, 23, 991-1008.
Scheen AJ, Mathieu C.- Recommandations 2012 en diabétologie. Prise en charge de l'hyperglycémie dans le diabéte de type 2 : une approche centrée sur le patient. Rev Med Liége, 2012, 67, 623-631.
Scheen AJ, Lefebvre PJ.- Insuline glargine et cancer: une tempête dans un verre d'eau ? Rev Med Liege, 2009, 64, 440-445.
Beck E, Scheen AJ.- Activité anticancéreuse de la metformine : nouvelles perspectives pour une vieille molécule. Rev Med Suisse, 2010, 6, 1601-1607.
Feng YH, Velazquez-Torres G, Gully C, et al.- The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth. J Cell Mol Med, 2011, 15, 825-836.
Emami Riedmaier A, Fisel P, Nies AT, et al.- Metformin and cancer : from the old medicine cabinet to pharmacological pitfalls and prospects. Trends Pharmacol Sci, 2013, 34, 126-135.
Pollak MN.- Investigating metformin for cancer prevention and treatment : the end of the beginning. Cancer Discovery, 2012, 2, 778-790.
Beck E, Scheen AJ.- Quels bénéfices anti-tumoraux attendre de la metformine ? Ann Endocrinol, 2013, 74, 137-147.
Scheen AJ, Ernest P, Jandrain B.- Comment j'explore... une différence de risque de survenue d'un événement dans les études cliniques. Rev Med Liege, 2012, 67, 597-602.
Stevens RJ, Ali R, Bankhead CR, et al.- Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. Diabetologia, 2012, 55, 2593-2603.
Decensi A, Puntoni M, Goodwin P, et al.- Metformin and cancer risk in diabetic patients : a systematic review and meta-analysis. Cancer Prev Res, 2010, 3, 1451-1461.
Noto H, Goto A, Tsujimoto T, et al.- Cancer risk in diabetic patients treated with metformin : a systematic review and meta-analysis. PLoS One, 2012, 7, e33411.
Soranna D, Scotti L, Zambon A, et al.- Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes : a meta-analysis. Oncologist, 2012, 17, 813-822.
Col NF, Ochs L, Springmann V, et al.- Metformin and breast cancer risk : a meta-analysis and critical literature review. Breast Cancer Res Treat, 2012, 135, 639-646.
Zhang ZJ, Zheng ZJ, Kan H, et al.- Reduced risk of colorectal cancer with metformin therapy in patients with type 2 diabetes : a meta-analysis. Diabetes Care, 2011, 34, 2323-2328.
Wang P, Kang D, Cao W, et al.- Diabetes mellitus and risk of hepatocellular carcinoma : a systematic review and meta-analysis. Diabetes Metab Res Rev, 2012, 28, 109-122.
Zhang H, Gao C, Fang L, et al.- Metformin and reduced risk of hepatocellular carcinoma in diabetic patients : a meta-analysis. Scand J Gastroenterol, 2013, 48, 78-87.
Zhang ZJ, Zheng ZJ, Shi R, et al.- Metformin for liver cancer prevention in patients with type 2 diabetes : a systematic review and meta-analysis. J Clin Endocrinol Metab, 2012, 97, 2347-2353.
Suissa S, Azoulay L.- Metformin and the risk of cancer : time-related biases in observational studies. Diabetes Care, 2012, 35, 2665-2673.
Duncan BB, Schmidt MI.- Metformin, cancer, alphabet soup, and the role of epidemiology in etiologic research. Diabetes Care, 2009, 32, 1748-1750.
Dowling RJ, Niraula S, Stambolic V, et al.- Metformin in cancer: translational challenges. J Mol Endocrinol, 2012, 48, R31-43.
Gallagher EJ, LeRoith D.- Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann N Y Acad Sci, 2011, 1243, 54-68.
Ben Sahra I, Le Marchand-Brustel Y, Tanti JF, et al. - Metformin in cancer therapy : a new perspective for an old antidiabetic drug? Mol Cancer Ther, 2010, 9, 1092-1099.
Papanas N, Maltezos E, Mikhailidis DP.- Metformin and cancer : licence to heal? Expert Opin Investig Drugs, 2010, 19, 913-917.
Martin M, Marais R.- Metformin : a diabetes drug for cancer, or a cancer drug for diabetics? J Clin Oncol, 2012, 30, 2698-2700.
Goodwin PJ, Stambolic V, Lemieux J, et al.- Evaluation of metformin in early breast cancer : a modification of the traditional paradigm for clinical testing of anti-cancer agents. Breast Cancer Res Treat, 2011, 126, 215-220.
Zhang P, Li H, Tan X, et al.- Association of metformin use with cancer incidence and mortality : a meta-analysis. Cancer Epidemiol, 2013, 37, 207-218.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.