[en] With the better management of cardiovascular risk factors, cancer plays an increasing role in the causes of death among patients with type 2 diabetes. 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 (sulfonylureas, insulin). Such beneficial effect is observed almost whatever the type of cancer, but seems to be more prominent in case of gastrointestinal and breast cancers. Several studies showed a significant relationship between the amplitude of the protection against cancer, on the one hand, and the daily dose of metformin and the duration of exposure, on the other hand. 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. Several meta-analyses recently confirmed that metformin therapy reduces the incidence of cancers and cancer-related mortality. 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. 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, independently of the presence of diabetes.
Disciplines :
Pharmacy, pharmacology & toxicology Oncology
Author, co-author :
Beck, Emmanuel
SCHEEN, André ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Language :
French
Title :
Quels benefices antitumoraux attendre de la metformine ?
Alternative titles :
[en] Which anti-tumour benefits to be expected from metformin?
Publication date :
2013
Journal title :
Annales d'Endocrinologie
ISSN :
0003-4266
eISSN :
2213-3941
Publisher :
Elsevier Masson, Paris, France
Volume :
74
Issue :
2
Pages :
137-47
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2013 Elsevier Masson SAS. All rights reserved.
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Bibliography
Giovannucci E., Harlan D.M., Archer M.C., Bergenstal R.M., Gapstur S.M., Habel L.A., et al. Diabetes and cancer: a consensus report. Diabetes Care 2010, 33:1674-1685.
Godsland I.F. Insulin resistance and hyperinsulinaemia in the development and progression of cancer. Clin Sci (Lond) 2010, 118:315-332.
Wysocki P.J., Wierusz-Wysocka B. Obesity, hyperinsulinemia and breast cancer: novel targets and a novel role for metformin. Expert Rev Mol Diagn 2010, 10:509-519.
Cohen D.H., LeRoith D. Obesity, type 2 diabetes, and cancer: the insulin and IGF connection. Endocr Relat Cancer 2012, 19:F27-F45.
Smith U., Gale E.A. Does diabetes therapy influence the risk of cancer?. Diabetologia 2009, 52:1699-1708.
Currie C.J., Poole C.D., Gale E.A. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 2009, 52:1766-1777.
Onitilo A.A., Engel J.M., Glurich I., Stankowski R.V., Williams G.M., Doi S.A. Diabetes and cancer II: role of diabetes medications and influence of shared risk factors. Cancer Causes Control 2012, 23:991-1008.
Inzucchi S.E., Bergenstal R.M., Buse J.B., Diamant M., Ferrannini E., Nauck M., et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2012, 55:1577-1596.
Lamanna C., Monami M., Marchionni N., Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2011, 13:221-228.
Boussageon R., Supper I., Bejan-Angoulvant T., Kellou N., Cucherat M., Boissel J.P., et al. Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. PLoS Med 2012, 9:e1001204.
Ben Sahra I., Le Marchand-Brustel Y., Tanti J.F., Bost F. Metformin in cancer therapy: a new perspective for an old antidiabetic drug?. Mol Cancer Ther 2010, 9:1092-1099.
Papanas N., Maltezos E., Mikhailidis D.P. Metformin and cancer: licence to heal?. Expert Opin Investig Drugs 2010, 19:913-917.
Evans J.M., Donnelly L.A., Emslie-Smith A.M., Alessi D.R., Morris A.D. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005, 330:1304-1305.
Feng Y.H., Velazquez-Torres G., Gully C., Chen J., Lee M.H., Yeung S.C. 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 A.T., Schaeffeler E., Schwab M. Metformin and cancer: from the old medicine cabinet to pharmacological pitfalls and prospects. Trends Pharmacol Sci 2013, 34:126-135.
Pollak M.N. Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov 2012, 2:778-790.
Beck E., Scheen A.J. Activité anticancéreuse de la metformine: nouvelles perspectives pour une vieille molécule. Rev Med Suisse 2010, 6:1601-1607.
Libby G., Donnelly L.A., Donnan P.T., Alessi D.R., Morris A.D., Evans J.M. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 2009, 32:1620-1625.
Qiu H., Rhoads G.G., Berlin J.A., Marcella S.W., Demissie K. Initial metformin or sulphonylurea exposure and cancer occurrence among patients with type 2 diabetes mellitus. Diabetes Obes Metab 2013, 15:349-357.
Redaniel M.T., Jeffreys M., May M.T., Ben-Shlomo Y., Martin R.M. Associations of type 2 diabetes and diabetes treatment with breast cancer risk and mortality: a population-based cohort study among British women. Cancer Causes Control 2012, 23:1785-1795.
Baur D.M., Klotsche J., Hamnvik O.P., Sievers C., Pieper L., Wittchen H.U., et al. Type 2 diabetes mellitus and medications for type 2 diabetes mellitus are associated with risk for and mortality from cancer in a German primary care cohort. Metabolism 2011, 60:1363-1371.
Ruiter R., Visser L.E., van Herk-Sukel M.P., Coebergh J.W., Haak H.R., Geelhoed-Duijvestijn P.H., et al. Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives: results from a large population-based follow-up study. Diabetes Care 2012, 35:119-124.
van Staa T.P., Patel D., Gallagher A.M., de Bruin M.L. Glucose-lowering agents and the patterns of risk for cancer: a study with the General Practice Research Database and secondary care data. Diabetologia 2012, 55:654-665.
Hsieh M.C., Lee T.C., Cheng S.M., Tu S.T., Yen M.H., Tseng C.H. The influence of type 2 diabetes and glucose-lowering therapies on cancer risk in the Taiwanese. Exp Diabetes Res 2012, 2012:413782.
Lee M.S., Hsu C.C., Wahlqvist M.L., Tsai H.N., Chang Y.H., Huang Y.C. 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. BMC Cancer 2011, 11:20.
Tseng C.H. Diabetes, metformin use, and colon cancer: a population-based cohort study in Taiwan. Eur J Endocrinol 2012, 167:409-416.
Lai S.W., Chen P.C., Liao K.F., Muo C.H., Lin C.C., Sung F.C. Risk of hepatocellular carcinoma in diabetic patients and risk reduction associated with anti-diabetic therapy: a population-based cohort study. Am J Gastroenterol 2012, 107:46-52.
Monami M., Lamanna C., Balzi D., Marchionni N., Mannucci E. Sulphonylureas and cancer: a case-control study. Acta Diabetol 2009, 46:279-284.
Monami M., Colombi C., Balzi D., Dicembrini I., Giannini S., Melani C., et al. Metformin and cancer occurrence in insulin-treated type 2 diabetic patients. Diabetes Care 2011, 34:129-131.
Li D., Yeung S.C., Hassan M.M., Konopleva M., Abbruzzese J.L. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology 2009, 137:482-488.
Hassan M.M., Curley S.A., Li D., Kaseb A., Davila M., Abdalla E.K., et al. Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma. Cancer 2010, 116:1938-1946.
Donadon V., Balbi M., Ghersetti M., Grazioli S., Perciaccante A., Della Valentina G., et al. Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease. World J Gastroenterol 2009, 15:2506-2511.
Donadon V., Balbi M., Valent F., Avogaro A. Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma. World J Gastroenterol 2010, 16:3025-3032.
Donadon V., Balbi M., Mas M.D., Casarin P., Zanette G. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease. Liver Int 2010, 30:750-758.
Chaiteerakij R., Yang J.D., Harmsen W.S., Slettedahl S.W., Mettler T.A., Fredericksen Z.S., et al. Risk factors for intrahepatic cholangiocarcinoma: association between metformin use and reduced cancer risk. Hepatology 2013, 57:648-655.
Wright J.L., Stanford J.L. Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study. Cancer Causes Control 2009, 20:1617-1622.
Bodmer M., Meier C., Krahenbuhl S., Jick S.S., Meier C.R. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care 2010, 33:1304-1308.
Bodmer M., Becker C., Meier C., Jick S.S., Meier C.R. Use of antidiabetic agents and the risk of pancreatic cancer: a case-control analysis. Am J Gastroenterol 2012, 107:620-626.
Bodmer M., Becker C., Meier C., Jick S.S., Meier C.R. Use of metformin is not associated with a decreased risk of colorectal cancer: a case-control analysis. Cancer Epidemiol Biomarkers Prev 2012, 21:280-286.
Bodmer M., Becker C., Meier C., Jick S.S., Meier C.R. Use of metformin and the risk of ovarian cancer: a case-control analysis. Gynecol Oncol 2011, 123:200-204.
Bodmer M., Becker C., Jick S.S., Meier C.R. Metformin does not alter the risk of lung cancer: a case-control analysis. Lung Cancer 2012, 78:133-137.
Azoulay L., Dell'Aniello S., Gagnon B., Pollak M., Suissa S. Metformin and the incidence of prostate cancer in patients with type 2 diabetes. Cancer Epidemiol Biomarkers Prev 2011, 20:337-344.
Smiechowski B.B., Azoulay L., Yin H., Pollak M.N., Suissa S. The use of metformin and the incidence of lung cancer in patients with type 2 diabetes. Diabetes Care 2013, 36:124-129.
Hitron A., Adams V., Talbert J., Steinke D. The influence of antidiabetic medications on the development and progression of prostate cancer. Cancer Epidemiol 2012, 36:e243-e250.
Bosco J.L., Antonsen S., Sorensen H.T., Pedersen L., Lash T.L. Metformin and incident breast cancer among diabetic women: a population-based case-control study in Denmark. Cancer Epidemiol Biomarkers Prev 2011, 20:101-111.
Home P.D., Kahn S.E., Jones N.P., Noronha D., Beck-Nielsen H., Viberti G. Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials. Diabetologia 2010, 53:1838-1845.
Chlebowski R.T., McTiernan A., Wactawski-Wende J., Manson J.E., Aragaki A.K., Rohan T., et al. Diabetes, metformin, and breast cancer in postmenopausal women. J Clin Oncol 2012, 30:2844-2852.
Stevens R.J., Ali R., Bankhead C.R., Bethel M.A., Cairns B.J., Camisasca R.P., 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., Cazzaniga M., Gennari A., Bonanni B., et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila) 2010, 3:1451-1461.
Noto H., Goto A., Tsujimoto T., Noda M. 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., Bosetti C., Grassi G., Catapano 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 N.F., Ochs L., Springmann V., Aragaki A.K., Chlebowski R.T. Metformin and breast cancer risk: a meta-analysis and critical literature review. Breast Cancer Res Treat 2012, 135:639-646.
Zhang Z.J., Zheng Z.J., Kan H., Song Y., Cui W., Zhao G., 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., Wang Y., Liu Z. 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., Zhao H.C., Yao S.K. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients: a meta-analysis. Scand J Gastroenterol 2013, 48:78-87.
Zhang Z.J., Zheng Z.J., Shi R., Su Q., Jiang Q., Kip K.E. 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.
Johnson J.A., Majumdar S.R., Simpson S.H., Toth E.L. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. Diabetes Care 2002, 25:2244-2248.
Monami M., Lamanna C., Pala L., Bardini G., Cresci B., Francesconi P., et al. Treatment with insulin secretagogues and cancer-related mortality in type 2 diabetic patients a retrospective cohort study. Exp Clin Endocrinol Diabetes 2008, 116:184-189.
Bo S., Ciccone G., Rosato R., Villois P., Appendino G., Ghigo E., et al. Cancer mortality reduction and metformin: a retrospective cohort study in type 2 diabetic patients. Diabetes Obes Metab 2012, 14:23-29.
Landman G.W., Kleefstra N., van Hateren K.J., Groenier K.H., Gans R.O., Bilo H.J. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care 2010, 33:322-326.
Currie C.J., Poole C.D., Jenkins-Jones S., Gale E.A., Johnson J.A., Morgan C.L. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care 2012, 35:299-304.
Bowker S.L., Yasui Y., Veugelers P., Johnson J.A. Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure. Diabetologia 2010, 53:1631-1637.
Hou G., Zhang S., Zhang X., Wang P., Hao X., Zhang J. Clinical pathological characteristics and prognostic analysis of 1,013 breast cancer patients with diabetes. Breast Cancer Res Treat 2013, 137:807-816.
Garrett C.R., Hassabo H.M., Bhadkamkar N.A., Wen S., Baladandayuthapani V., Kee B.K., et al. Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer. Br J Cancer 2012, 106:1374-1378.
Lee J.H., Kim T.I., Jeon S.M., Hong S.P., Cheon J.H., Kim W.H. The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. Int J Cancer 2012, 131:752-759.
Chen T.M., Lin C.C., Huang P.T., Wen C.F. Metformin associated with lower mortality in diabetic patients with early stage hepatocellular carcinoma after radiofrequency ablation. J Gastroenterol Hepatol 2011, 26:858-865.
Sadeghi N., Abbruzzese J.L., Yeung S.C., Hassan M., Li D. Metformin use is associated with better survival of diabetic patients with pancreatic cancer. Clin Cancer Res 2012, 18:2905-2912.
He X.X., Tu S.M., Lee M.H., Yeung S.C. Thiazolidinediones and metformin associated with improved survival of diabetic prostate cancer patients. Ann Oncol 2011, 22:2640-2645.
Spratt D.E., Zhang C., Zumsteg Z.S., Pei X., Zhang Z., Zelefsky M.J. Metformin and prostate cancer: reduced development of castration-resistant disease and prostate cancer mortality. Eur Urol 2013, 63:709-716.
He X., Esteva F.J., Ensor J., Hortobagyi G.N., Lee M.H., Yeung S.C. Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer. Ann Oncol 2012, 23:1771-1780.
Bayraktar S., Hernadez-Aya L.F., Lei X., Meric-Bernstam F., Litton J.K., Hsu L., et al. Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer. Cancer 2012, 118:1202-1211.
Suissa S., Azoulay L. Metformin and the risk of cancer: time-related biases in observational studies. Diabetes Care 2012, 35:2665-2673.
Duncan B.B., Schmidt M.I. Metformin, cancer, alphabet soup, and the role of epidemiology in etiologic research. Diabetes Care 2009, 32:1748-1750.
Johnson J.A., Bowker S.L. Intensive glycaemic control and cancer risk in type 2 diabetes: a meta-analysis of major trials. Diabetologia 2011, 54:25-31.
Martin M., Marais R. Metformin: a diabetes drug for cancer, or a cancer drug for diabetics?. J Clin Oncol 2012, 30:2698-2700.
Liu H., Scholz C., Zang C., Schefe J.H., Habbel P., Regierer A.C., et al. Metformin and the mTOR inhibitor everolimus (RAD001) sensitize breast cancer cells to the cytotoxic effect of chemotherapeutic drugs in vitro. Anticancer Res 2012, 32:1627-1637.
Cufi S., Corominas-Faja B., Vazquez-Martin A., Oliveras-Ferraros C., Dorca J., Bosch-Barrera J., et al. Metformin-induced preferential killing of breast cancer initiating CD44+CD24-/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts. Oncotarget 2012, 3:395-398.
Niraula S., Dowling R.J., Ennis M., Chang M.C., Done S.J., Hood N., et al. Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study. Breast Cancer Res Treat 2012, 135:821-830.
Goodwin P.J., Stambolic V., Lemieux J., Chen B.E., Parulekar W.R., Gelmon K.A., 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.
Goodwin P.J., Ligibel J.A., Stambolic V. Metformin in breast cancer: time for action. J Clin Oncol 2009, 27:3271-3273.
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