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Journal of Endocrinological Investigation
Published in: Journal of Endocrinological Investigation 10/2015

01-10-2015 | Short Review

Expanding the therapeutic spectrum of metformin: from diabetes to cancer

Authors: F. Coperchini, P. Leporati, M. Rotondi, L. Chiovato

Published in: Journal of Endocrinological Investigation | Issue 10/2015

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Abstract

Introduction

Metformin, an oral hypoglycemic agent, was introduced in the clinical practice for the treatment of type 2 diabetes mellitus more than a half-century ago. Over the years, several studies demonstrated that diabetic patients treated with metformin have a lower incidence of cancer, raising the hypothesis that the spectrum of clinical applications of the drug could be expanded also to cancer therapy. Following these initial findings, a large number of studies were performed aimed at elucidating the effects of metformin on different types of tumor, at explaining its direct and indirect anti-cancer mechanisms and at identifying the molecular pathways targeted by the drug. Several clinical trials were also performed aimed at evaluating the potential anti-cancer effect of metformin among diabetic and non-diabetic patients affected by different types of cancer. While the results of several clinical studies are encouraging, a considerable number of other investigations do not support a role of metformin as an anti-cancer agent, and highlight variables possibly accounting for discrepancies.

Aim

We hereby review the results of in vitro and in vivo studies addressing the issue of the anti-cancer effects of metformin.

Conclusions

If in vitro data appear solid, the results provided by in vivo studies are somehow controversial. In this view, larger studies are needed to fully elucidate the role of metformin on cancer development and progression, as well as the specific clinical settings in which metformin could become an anti-cancer drug.
Literature
1.
Bailey CJ, Day C (2004) Metformin: its botanical background. Pract Diab Int 21:115–117CrossRef
2.
Malek M, Aghili R, Emami Z, Khamseh ME (2013) Risk of cancer in diabetes: the effect of metformin. ISRN Endocrinol 2013:636927PubMedCentralPubMed
3.
Inzucchi SE, Maggs DG, Spollett GR, Page SL, Rife FS, Walton V, Shulman GI (1998) Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 338:867–872CrossRefPubMed
4.
Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, Zhou G, Williamson JM, Ljunqvist O, Efendic S, Moller DE, Thorell A, Goodyear LJ (2002) Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51:2074–2081CrossRefPubMed
5.
Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE (1995) Metabolic effects of metformin in noninsulin-dependent diabetes mellitus. N Engl J Med 333:550–554CrossRefPubMed
6.
7.
Glintborg D, Mumm H, Altinok ML, Richelsen B, Bruun JM, Andersen M (2014) Adiponectin, interleukin-6, monocyte chemoattractant protein-1, and regional fat mass during 12-month randomized treatment with metformin and/or oral contraceptives in polycystic ovary syndrome. J Endocrinol Invest 37:757–764CrossRefPubMed
8.
Ghazeeri G, Abbas HA, Skaff B, Harajly S, Awwad J (2015) Inadequacy of initiating rosuvastatin then metformin on biochemical profile of polycystic ovarian syndrome patients. J Endocrinol Invest [Epub ahead of print]
9.
10.
Esteghamati A, Rezvani S, Khajeh E, Ebadi M, Nakhjavani M, Noshad S (2014) Comparative effects of metformin and pioglitazone on YKL-40 in type 2 diabetes: a randomized clinical trial. J Endocrinol Invest (epub ahead of print)
11.
Cappelli C, Rotondi M, Pirola I, Agosti B, Formenti A, Zarra E, Valentini U, Leporati P, Chiovato L, Castellano M (2012) Thyreotropin levels in diabetic patients on metformin treatment. Eur J Endocrinol 167:261–265PubMed
12.
Rotondi M, Cappelli C, Magri F, Botta R, Dionisio R, Iacobello C, De Cata P, Nappi RE, Castellano M, Chiovato L (2011) Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome. Clin Endocrinol (Oxf) 75:378–381CrossRef
13.
Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348:1625–1638CrossRefPubMed
14.
Novosyadlyy R, Lann DE, Vijayakumar A, Rowzee A, Lazzarino DA, Fierz Y, Carboni JM, Gottardis MM, Pennisi PA, Molinolo AA, Kurshan N, Mejia W, Santopietro S, Yakar S, Wood TL, LeRoith D (2010) Insulin mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes. Cancer Res 70:741–751CrossRefPubMedCentralPubMed
15.
Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R (2009) Diabetes and cancer. Endocr Relat Cancer 16:1103–1123CrossRefPubMed
16.
17.
Bowker SL, Majumdar SR, Veugelers P, Johnson JA (2006) Increased cancerrelated mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 29:254–258CrossRefPubMed
18.
Bo S, Benso A, Durazzo M, Ghigo E (2012) Does use of metformin protect against cancer in type 2 diabetes mellitus? J Endocrinol Invest 35:231–235CrossRefPubMed
19.
Mei ZB, Zhang ZJ, Liu CY, Liu Y, Cui A, Liang ZL, Wang GH, Cui L (2014) Survival benefits of metformin for colorectal cancer patients with diabetes: a systematic review and meta-analysis. PLoS One 9:e91818CrossRefPubMedCentralPubMed
20.
Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A (2013) Metformin therapy and risk of cancer in patients with type 2 diabetes. PLoS One 8:e71583CrossRefPubMedCentralPubMed
21.
Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167–1174CrossRefPubMedCentralPubMed
22.
23.
El-Mir MY, Nogueira V, Fontaine E, Avéret N, Rigoulet M, Leverve X (2000) Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 275:223–228CrossRefPubMed
24.
Owen MR, Doran E, Halestrap AP (2000) Evidence that metformin exerts its antidiabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 348:607–614CrossRefPubMedCentralPubMed
25.
Hardie DG, Ross FA, Hawley SA (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 13:251–262CrossRefPubMed
26.
Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M, Cantley LC (2005) The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310:1642–1646CrossRefPubMedCentralPubMed
27.
Towler MC, Hardie DG (2007) AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res 100:328–341CrossRefPubMed
28.
Hadad S, Iwamoto T, Jordan L, Purdie C, Bray S, Baker L, Jellema G, Deharo S, Hardie DG, Pusztai L, Moulder-Thompson S, Dewar JA, Thompson AM (2011) Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat 128:783–794CrossRefPubMed
29.
Campagnoli C, Pasanisi P, Abbà C, Ambroggio S, Biglia N, Brucato T, Colombero R, Danese S, Donadio M, Venturelli E, Zito G, Berrino F (2012) Effect of different doses of metformin on serum testosterone and insulin in non-diabetic women with breast cancer: a randomized study. Clin Breast Cancer 12:175–182CrossRefPubMed
30.
Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N (2007) Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res 67:10804–10812CrossRefPubMed
31.
Kalender A, Selvaraj A, Kim SY, Gulati P, Brûlé S, Viollet B, Kemp BE, Bardeesy N, Dennis P, Schlager JJ, Marette A, Kozma SC, Thomas G (2010) Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase dependent manner. Cell Metab 11:390–401CrossRefPubMedCentralPubMed
32.
Saeedi R, Parsons HL, Wambolt RB, Paulson K, Sharma V, Dyck JR, Brownsey RW, Allard MF (2008) Metabolic actions of metformin in the heart can occur by AMPK independent mechanisms. Am J Physiol Heart Circ Physiol 294:2497–2506CrossRef
33.
Treins C, Murdaca J, Van Obberghen E, Giorgetti-Peraldi S (2006) AMPK activation inhibits the expression of HIF-1alpha induced by insulin and IGF-1. Biochem Biophys Res Commun 342:1197–1202CrossRefPubMed
34.
Chiang GG, Abraham RT (2007) Targeting the mTOR signaling network in cancer. Trends Mol Med 13:433–442CrossRefPubMed
35.
Inoki K, Zhu T, Guan KL (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115:577–590CrossRefPubMed
36.
37.
Foretz M, Hébrard S, Leclerc J, Zarrinpashneh E, Soty M, Mithieux G, Sakamoto K, Andreelli F, Viollet B (2010) Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest 120:2355–2369CrossRefPubMedCentralPubMed
38.
Scotland S, Saland E, Skuli N, de Toni F, Boutzen H, Micklow E, Sénégas I, Peyraud R, Peyriga L, Théodoro F, Dumon E, Martineau Y, Danet-Desnoyers G, Bono F, Rocher C, Levade T, Manenti S, Junot C, Portais JC, Alet N, Récher C, Selak MA, Carroll M, Sarry JE (2013) Mitochondrial energetic and AKT status mediate metabolic effects and apoptosis of metformin in human leukemic cells. Leukemia 27:2129–2138CrossRefPubMed
39.
Ben Sahra I, Regazzetti C, Robert G, Laurent K, Le Marchand-Brustel Y, Auberger P, Tanti JF, Giorgetti-Peraldi S, Bost F (2011) Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res 71:4366–4372CrossRefPubMed
40.
Corominas-Faja B, Quirantes-Piné R, Oliveras-Ferraros C, Vazquez-Martin A, Cufí S, Martin-Castillo B, Micol V, Joven J, Segura-Carretero A, Menendez JA (2012) Metabolomic fingerprint reveals that metformin impairs onecarbon metabolism in a manner similar to the antifolate class of chemotherapy drugs. Aging (Albany NY) 4:480–498
41.
42.
Gerondakis S, Fulford TS, Messina NL, Grumont RJ (2014) NF-κB control of T cell development. Nat Immunol 15:15–25CrossRefPubMed
43.
Hattori Y, Suzuki K, Hattori S, Kasai K (2006) Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension 47:1183–1188CrossRefPubMed
44.
Isoda K, Young JL, Zirlik A, MacFarlane LA, Tsuboi N, Gerdes N, Schönbeck U, Libby P (2006) Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells. Arterioscler Thromb Vasc Biol 26:611–617CrossRefPubMed
45.
Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M (2006) Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res 66:10269–10273CrossRefPubMed
46.
Carmignani M, Volpe AR, Aldea M, Soritau O, Irimie A, Florian IS, Tomuleasa C, Baritchii A, Petrushev B, Crisan G, Valle G (2014) Glioblastoma stem cells: a new target for metformin and arsenic trioxide. J Biol Regul Homeost Agents 28:1–15PubMed
47.
Queiroz EA, Puukila S, Eichler R, Sampaio SC, Forsyth HL, Lees SJ, Barbosa AM, Dekker RF, Fortes ZB, Khaper N (2014) Metformin induces apoptosis and cell cycle arrest mediated by oxidative stress, AMPK and FOXO3a in MCF-7 breast cancer cells. PLoS One 9:e98207CrossRefPubMedCentralPubMed
48.
Buzzai M, Jones RG, Amaravadi RK, Lum JJ, DeBerardinis RJ, Zhao F, Viollet B, Thompson CB (2007) Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res 67:6745–6752CrossRefPubMed
49.
Erices R, Bravo ML, Gonzalez P, Oliva B, Racordon D, Garrido M, Ibañez C, Kato S, Brañes J, Pizarro J, Barriga MI, Barra A, Bravo E, Alonso C, Bustamente E, Cuello MA, Owen GI (2013) Metformin, at concentrations corresponding to the treatment of diabetes, potentiates the cytotoxic effects of carboplatin in cultures of ovarian cancer cells. Reprod Sci 20:1433–1446CrossRefPubMedCentralPubMed
50.
Wang LW, Li ZS, Zou DW, Jin ZD, Gao J, Xu GM (2008) Metformin induces apoptosis of pancreatic cancer cells. World J Gastroenterol 14:7192–7198CrossRefPubMed
51.
Ashinuma H, Takiguchi Y, Kitazono S, Kitazono-Saitoh M, Kitamura A, Chiba T, Tada Y, Kurosu K, Sakaida E, Sekine I, Tanabe N, Iwama A, Yokosuka O, Tatsumi K (2012) Antiproliferative action of metformin in human lung cancer cell lines. Oncol Rep 28:8–14PubMed
52.
Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, Tanti JF, Le Marchand-Brustel Y, Bost F (2008) The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene 27:3576–3586CrossRefPubMed
53.
Fujihara S, Kato K, Morishita A, Iwama H, Nishioka T, Chiyo T, Nishiyama N, Miyoshi H, Kobayashi M, Kobara H, Mori H, Okano K, Suzuki Y, Masaki T (2015) Antidiabetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo. Int J Oncol 46:2172–2180PubMed
54.
Bao B, Wang Z, Ali S, Ahmad A, Azmi AS, Sarkar SH, Banerjee S, Kong D, Li Y, Thakur S, Sarkar FH (2012) Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells. Cancer Prev Res (Phila) 5:355–364CrossRef
55.
Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715CrossRefPubMedCentralPubMed
56.
Moreno-Bueno G, Peinado H, Molina P, Olmeda D, Cubillo E, Santos V, Palacios J, Portillo F, Cano A (2009) The morphological and molecular features of the epithelial-to-mesenchymal transition. Nat Protoc 4:1591–1613CrossRefPubMed
57.
Sarrió D, Rodriguez-Pinilla SM, Hardisson D, Cano A, Moreno-Bueno G, Palacios J (2008) Epithelialmesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res 68:989–997CrossRefPubMed
58.
Vazquez-Martin A, Oliveras-Ferraros C, Cufí S, Del Barco S, Martin-Castillo B, Menendez JA (2010) Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status. Cell Cycle 9:3807–3814CrossRefPubMed
59.
Wang Y, Yao B, Wang Y, Zhang M, Fu S, Gao H, Peng R, Zhang L, Tang J (2014) Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer. Int J Mol Med 33:1514–1522PubMed
60.
Cerezo M, Tichet M, Abbe P, Ohanna M, Lehraiki A, Rouaud F, Allegra M, Giacchero D, Bahadoran P, Bertolotto C, Tartare-Deckert S, Ballotti R, Rocchi S (2013) Metformin blocks melanoma invasion and metastasis development in AMPK/p53-dependent manner. Mol Cancer Ther 12:1605–1615CrossRefPubMed
61.
Cifarelli V, Lashinger LM, Devlin KL, Dunlap SM, Huang J, Kaaks R, Pollak MN, Hursting SD (2015) Metformin and rapamycin reduce pancreatic cancer growth in obese prediabetic mice by distinct microRNA-regulated mechanisms. Diabetes 64:1632–1642CrossRefPubMed
62.
Tan BK, Adya R, Chen J, Lehnert H, Sant Cassia LJ, Randeva HS (2011) Metformin treatment exerts antiinvasive and antimetastatic effects in human endometrial carcinoma cells. J Clin Endocrinol Metab 96:808–816CrossRefPubMed
63.
Tan XL, Bhattacharyya KK, Dutta SK, Bamlet WR, Rabe KG, Wang E, Smyrk TC, Oberg AL, Petersen GM, Mukhopadhyay D (2015) Metformin suppresses pancreatic tumor growth with inhibition of NFκB/STAT3 inflammatory signaling. Pancreas 44:636–647CrossRefPubMed
64.
Rotondi M, Coperchini F, Pignatti P, Magri F, Chiovato L (2015) Metformin reverts the secretion of CXCL8 induced by TNF-α in primary cultures of human thyroid cells: an additional indirect anti-tumor effect of the drug. J Clin Endocrinol Metab 100:E427–E432CrossRefPubMed
65.
Rotondi M, Coperchini F, Chiovato L (2013) CXCL8 in thyroid disease: from basic notions to potential applications in clinical practice. Cytokine Growth Factor Rev 24:539–546CrossRefPubMed
66.
Bodmer M, Meier C, Krähenbühl S, Jick SS, Meier CR (2010) Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care 33:1304–1308CrossRefPubMedCentralPubMed
67.
Bosco JL, Antonsen S, Sørensen HT, Pedersen L, Lash TL (2011) Metformin and incident breast cancer among diabetic women: a population-based case–control study in Denmark. Cancer Epidemiol Biomark Prev 20:101–111CrossRef
68.
Lee JH, Kim TI, Jeon SM, Hong SP, Cheon JH, Kim WH (2012) The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. Int J Cancer 131:752–759CrossRefPubMed
69.
Tan BX, Yao WX, Ge J, Peng XC, Du XB, Zhang R, Yao B, Xie K, Li LH, Dong H, Gao F, Zhao F, Hou JM, Su JM, Liu JY (2011) Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes. Cancer 117:5103–5111CrossRefPubMed
70.
Baur DM, Klotsche J, Hamnvik OP, Sievers C, Pieper L, Wittchen HU, Stalla GK, Schmid RM, Kales SN, Mantzoros CS (2011) 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 60:1363–1371
71.
Monami M, Colombi C, Balzi D, Dicembrini I, Giannini S, Melani C, Vitale V, Romano D, Barchielli A, Marchionni N, Rotella CM, Mannucci E (2011) Metformin and cancer occurrence in insulintreated type 2 diabetic patients. Diabetes Care 34:129–131CrossRefPubMedCentralPubMed
72.
Leone A, Di Gennaro E, Bruzzese F, Avallone A, Budillon A (2014) New perspective for an old antidiabetic drug: metformin as anticancer agent. Cancer Treat Res 159:355–376CrossRefPubMed
73.
Yin M, Zhou J, Gorak EJ, Quddus F (2013) Metformin is associated with survival benefit in cancer patients with concurrent type 2 diabetes: a systematic review and meta-analysis. Oncologist 18:1248–1255CrossRefPubMedCentralPubMed
74.
Sehdev A, Shih YC, Vekhter B, Bissonnette MB, Olopade OI, Polite BN (2015) Metformin for primary colorectal cancer prevention in patients with diabetes: a case–control study in a US population. Cancer 121:1071–1078CrossRefPubMed
75.
Lee CK, Jung M, Jung I, Heo SJ, Jeong YH, An JY, Kim HI, Cheong JH, Hyung WJ, Noh SH, Kim HS, Rha SY, Chung HC (2015) Cumulative metformin use and its impact on survival in gastric cancer patients after gastrectomy. Ann Surg (epub ahead of print)
76.
Klubo-Gwiezdzinska J, Costello J Jr, Patel A, Bauer A, Jensen K, Mete M, Burman KD, Wartofsky L, Vasko V (2013) Treatment with metformin is associated with higher remission rate in diabetic patients with thyroid cancer. J Clin Endocrinol Metab 98:3269–3279CrossRefPubMed
77.
78.
Goodwin PJ, Parulekar WR, Gelmon KA, Shepherd LE, Ligibel JA, Hershman DL, Rastogi P, Mayer IA, Hobday TJ, Lemieux J, Thompson AM, Pritchard KI, Whelan TJ, Mukherjee SD, Chalchal HI, Oja CD, Tonkin KS, Bernstein V, Chen BE, Stambolic V (2015) Effect of metformin vs placebo on and metabolic factors in NCIC CTG MA.32. J Natl Cancer Inst 4:107(3)
79.
Niraula S, Dowling RJ, Ennis M, Chang MC, Done SJ, Hood N, Escallon J, Leong WL, McCready DR, Reedijk M, Stambolic V, Goodwin PJ (2012) Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study. Breast Cancer Res Treat 135:821–830CrossRefPubMed
80.
Dowling RJ, Niraula S, Chang MC, Done SJ, Ennis M, McCready DR, Leong WL, Escallon JM, Reedijk M, Goodwin PJ, Stambolic V (2015) Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study. Breast Cancer Res 3:17–32
81.
Cazzaniga M, DeCensi A, Pruneri G, Puntoni M, Bottiglieri L, Varricchio C, Guerrieri-Gonzaga A, Gentilini OD, Pagani G, Dell’Orto P, Lazzeroni M, Serrano D, Viale G, Bonanni B (2013) The effect of metformin on apoptosis in a breast cancer presurgical trial. Br J Cancer 109:2792–2797CrossRefPubMedCentralPubMed
82.
DeCensi A, Puntoni M, Gandini S, Guerrieri-Gonzaga A, Johansson HA, Cazzaniga M, Pruneri G, Serrano D, Schwab M, Hofmann U, Mora S, Aristarco V, Macis D, Bassi F, Luini A, Lazzeroni M, Bonanni B, Pollak MN (2014) Differential effects of metformin on breast cancer proliferation according to markers of insulin resistance and tumor subtype in a randomized presurgical trial. Breast Cancer Res Treat 148:81–90CrossRefPubMedCentralPubMed
83.
Oppong BA, Pharmer LA, Oskar S, Eaton A, Stempel M, Patil S, King TA (2014) The effect of metformin on breast cancer outcomes in patients with type 2 diabetes. Cancer Med 3:1025–1034CrossRefPubMedCentralPubMed
84.
Ko EM, Stürmer T, Hong JL, Castillo WC, Bae-Jump V, Funk MJ (2015) Metformin and the risk of endometrial cancer: a population-based cohort study. Gynecol Oncol 136:341–347CrossRefPubMed
85.
Luo J, Beresford S, Chen C, Chlebowski R, Garcia L, Kuller L, Regier M, Wactawski-Wende J, Margolis KL (2014) Association between diabetes, diabetes treatment and risk of developing endometrial cancer. Br J Cancer 111:1432–1439CrossRefPubMed
86.
Sakoda LC, Ferrara A, Achacoso NS, Peng T, Ehrlich SF, Quesenberry CP Jr, Habel LA (2015) Metformin use and lung cancer risk in patients with diabetes. Cancer Prev Res (Phila) 8:174–179
87.
Merrick GS, Bennett A, Couture T, Butler WM, Galbreath RW, Adamovich E (2015) Metformin does not predict for prostate cancer diagnosis, grade, or volume of disease after transperineal template-guided mapping biopsy. Am J Clin Oncol (epub ahead of print)
88.
Soffer D, Shi J, Chung J, Schottinger JE, Wallner LP, Chlebowski RT, Lentz SE, Haque R (2015) Metformin and breast and gynecological cancer risk among women with diabetes. BMJ Open Diabetes Res Care 3:e000049CrossRefPubMedCentralPubMed
89.
Suissa S, Azoulay L (2014) Metformin and cancer: mounting evidence against an association. Diabetes Care 37:1786–1788CrossRefPubMed
90.
Gandini S, Puntoni M, Heckman-Stoddard BM, Dunn BK, Ford L, DeCensi A, Szabo E (2014) Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders. Cancer Prev Res (Phila) 7:867–885CrossRef
91.
Tsilidis KK, Capothanassi D, Allen NE, Rizos EC, Lopez DS, van Veldhoven K, Sacerdote C, Ashby D, Vineis P, Tzoulaki I, Ioannidis JP (2014) Metformin does not affect cancer risk: a cohort study in the U.K. Clinical practice research datalink analyzed like an intention-to-treat trial. Diabetes Care 37:2522–2532CrossRefPubMed
92.
Kowall B, Rathmann W, Kostev K (2015) Are sulfonylurea and insulin therapies associated with a larger risk of cancer than metformin therapy? A retrospective database analysis. Diabetes Care 38:59–65CrossRefPubMed
93.
Vissers PA, Cardwell CR, van de Poll-Franse LV, Young IS, Pouwer F, Murray LJ (2015) The association between glucose-lowering drug use and mortality among breast cancer patients with type 2 diabetes. Breast Cancer Res Treat 150:427–437CrossRefPubMed
94.
Decensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B, Gandini S (2010) Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila) 3:1451–1461CrossRef
Metadata
Title
Expanding the therapeutic spectrum of metformin: from diabetes to cancer
Authors
F. Coperchini
P. Leporati
M. Rotondi
L. Chiovato
Publication date
01-10-2015
Publisher
Springer International Publishing
Published in
Journal of Endocrinological Investigation / Issue 10/2015
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-015-0370-z

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Keynote webinar | Spotlight on medication adherence

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

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