Diabetes Mellitus, Type 2/drug therapy; Humans; Hypoglycemic Agents/therapeutic use; Metformin/therapeutic use; Neoplasms/epidemiology/prevention & control
Abstract :
[en] Type 2 diabetes is associated with a higher risk of cancer, which appears more obvious since the reduction of cardiovascular mortality. All glucose-lowering oral agents do not have the same impact on cancer: the risk is increased with sulfonylureas and decreased with metformin (and glitazones). Numerous epidemiological observational and case-control studies showed that metformin is associated with a lower incidence of cancer and a lower cancer-related death rate. A dose-response relationship and a relation between duration of prior treatment with metformin and the protective effect against cancer have been reported. Mechanisms involved are the activation of the AMPK enzyme and the inhibition of the mTOR pathway. Studies with metformin are ongoing in the field of oncology, especially as adjunct to treatment of breast cancer. [fr] Le diabète de type 2 est associé à un risque accru de cancer, d’autant plus évident qu’on
maîtrise mieux la mortalité cardio-vasculaire. Tous les traitements antidiabétiques n’ont pas le
même impact sur le cancer : le risque est accru avec les sulfonylurées et diminué avec la
metformine (et les glitazones). De nombreuses études épidémiologiques observationnelles et
cas-témoins récentes révèlent qu’un traitement par metformine est associé à une nette
réduction de l’incidence de néoplasies et de la mortalité par cancer. Il existe une relation doseréponse
et une relation entre la durée préalable du traitement par metformine et l’effet
protecteur observé. Les mécanismes invoqués sont l’activation de l’enzyme AMPK et
l’inhibition de la voie mTOR. Des études avec la metformine sont en cours en oncologie,
notamment dans le cancer du sein.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Beck, Emmanuel ; Centre Hospitalier Universitaire de Liège - CHU > Frais communs médecine
Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Language :
French
Title :
Activite anticancereuse de la metformine: nouvelles perspectives pour une vieille molecule.
Alternative titles :
[en] Anti-cancer activity of metformin: new perspectives for an old drug
Vigneri P, Frasca F, Sciacca L, et al. Diabetes and cancer. Endocr Relat Cancer 2009;16:1103-23.
** Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: A consensus report. Diabetes Care 2010;33:1674-85.
Schott S, Schneeweiss A, Sohn C. Breast cancer and diabetes mellitus. Exp Clin Endocrinol Diabetes 2010 Jun 8, epub ahead of print.
Renehan AG, Roberts DL, Dive C. Obesity and cancer: Pathophysiological and biological mechanisms. Arch Physiol Biochem 2008;114:71-83. (Pubitemid 351998746)
* Godsland IF. Insulin resistance and hyperinsulinaemia in the development and progression of cancer. Clin Sci 2010;118:315-32.
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 2009;324:626-31.
Wysocki PJ, Wierusz-Wysocka B. Obesity, hyperinsulinemia and breast cancer: Novel targets and a novel role for metformin. Expert Rev Mol Diagn 2010; 10:509-19.
Scheen AJ, Paquot N. Approche multirisque du patient diabétique de type 2: désaccord sur les valeurs cibles suite à l'étude ACCORD. Rev Med Suisse 2010; 6:1582-7.
Barone BB, Yeh HC, Snyder CF, et al. Postoperative mortality in cancer patients with preexisting diabetes: Systematic review and meta-analysis. Diabetes Care 2010;33:931-9.
* Barone BB, Yeh HC, Snyder CF, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: A systematic review and meta-analysis. JAMA 2008;300:2754-64.
** Smith U, Gale EAM. Does diabetes therapy influence the risk of cancer? Diabetologia 2009;52:1699-708.
* Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 2009;52:1766-77.
Scheen AJ, Lefèbvre PJ. La metformine: des effets métaboliques aux indications thérapeutiques. Med Hyg 1993;51:1993-8.
Scheen AJ. Current management of coexisting obesity and type 2 diabetes. Drugs 2003;63:1165-84.
Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycaemia in type 2 diabetes: 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. Diabetologia 2009;52:17-30.
Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-89.
Kooy A, de Jager J, Lehert P, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med 2009;169:616-25.
Mannucci E, Monami M, Balzi D, et al. Doses of insulin and its analogues and cancer occurrence in insulin-treated type 2 diabetic patients. Diabetes Care 2010, June 14, epub ahead of print.
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 2010 May 3, epub ahead of print.
* Ben Sahra I, Le Marchand-Brustel Y, Tanti JF, Bost F. Metformin in cancer therapy: A new perspective for an old antidiabetic drug? Mol Cancer Ther 2010;9:1092-9.
Papanas N, Maltezos E, Mikhailidis DP. Metformin and cancer: Licence to heal? Expert Opin Investig Drugs 2010 Jun 18, epub ahead of print.
Libby G, Donnelly LA, Donnan PT, et al. New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes. Diabetes Care 2009;32:1620-5.
Evans JM, Donnelly LA, Emslie-Smith AM, et al. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005;330:1304-5.
Monami M, Lamanna C, Balzi D, et al. Sulphonylureas and cancer: A case-control study. Acta Diabetol 2009;46:279-84.
Li D, Yeung SC, Hassan MM, et al. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology 2009;137:482-8.
Hassan MM, Curley SA, Li D, Kaseb A, et al. Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma. Cancer 2010;116: 1938-46.
Donadon V, Balbi M, Ghersetti M, et al. Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease. World J Gastroenterol 2009; 15:2506-11.
Donadon V, Balbi M, Valent F, Avogaro A. Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma. World J Gastroenterol 2010;16:3025-32.
Donadon V, Balbi M, Mas MD, Casarin P, Zanette G. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease. Liver Int 2010;30:750-8.
Wright JL, Stanford JL, et al. Metformin use and prostate cancer in Caucasian men: Results from a population-based case-control study. Cancer Causes Control 2009;20:1617-22.
Bodmer M, Meier C, Krähenbühl S, et al. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care 2010;33:1304-8.
Home PD, Kahn SE, Jones NP, et al. 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 Jun 8, epub ahead of print.
Johnson JA, Majumdar SR, Simpson SH, Toth EL. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. Diabetes Care 2002;25:2244-8.
Monami M, Lamanna C, Pala L, et al. Treatment with insulin secretagogues and cancer-related mortality in type 2 diabetic patients a retrospective cohort study. Exp Clin Endocrinol Diabetes 2008;116:184-9.
Landman GW, Kleefstra N, van Hateren KJ, et al. Metformin associated with lower cancer mortality in type 2 diabetes (ZODIAC-16). Diabetes Care 2009;33: 322-6.
Bowker SL, et al. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006;29:254-8.
Bowker SL, Yasui Y, Veugelers P, Johnson JA. Glucose-lowering agents and cancer mortality rates in type 2 diabetes: Assessing effects of time-varying exposure. Diabetologia 2010;53:1631-7.
Monami M, Lamanna C, Marchionni N, Mannucci E. Rosiglitazone and risk of cancer: A meta-analysis of randomized clinical trials. Diabetes Care 2008;31:1455-60.
Monami M, Balzi D, Lamanna C, et al. Are sulphonylureas all the same? A cohort study on cardiovascular and cancer-related mortality. Diabetes Metab Res Rev 2007;23:479-84.
* Duncan BB, Schmidt MI. Metformin, cancer, alphabet soup, and the role of epidemiology in etiologic research. Diabetes Care 2009;32:1748-50.
Pollak M. Insulin and insulin-like growth factor signaling in neoplasia. Nat Rev Cancer 2008;:915-28.
Fay JR, Steele V, Crowell JA. Energy homeostasis and cancer prevention: The AMP-activated protein kinase. Cancer Prev Res 2009;2:301-9.
Kalender A, Selvaraj A, Kim SY, et al. Metformin, independent of AMPK, inhibits mTORCI in a rag GTPase-dependent manner. Cell Metab 2010;11:390-401.
Rice S, Pellatt L, Ramanathan K, et al. Metformin inhibits aromatase via an extracellular signal-regulated kinase-mediated pathway. Endocrinology 2009;150:4794-801.
Jiralerspong S, Palla SL, Giordano SH, et al. Treatment with metformin gives better response to chemotherapy of breast cancer. J Clin Oncol 2009;27:3297-302.
Goodwin PJ, Ligibel JA, Stambolic V. Metformin in breast cancer: Time for action. J Clin Oncol 2009;27: 3271-3.