Metformina: más allá del control glucémico
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Cómo citar

Morantes-Caballero, J. A., Londoño-Zapata, G. A., Rubio-Rivera, M., & Pinilla-Roa, A. E. (2017). Metformina: más allá del control glucémico. Médicas UIS, 30(1), 57–71. https://doi.org/10.18273/revmed.v30n1-2017005

Resumen

La metformina es una biguanida que disminuye gluconeogénesis e incrementa la recaptación de glucosa en los músculos, sin embargo, más allá del glucémico se han documentado beneficios adicionales como la disminución de complicaciones crónicas derivadas de la hiperglucemia, entre ellas las cardiovasculares y del síndrome metabólico per se. Objetivo: identificar los efectos de la metformina diferentes al control control glucémico en población con diabetes mellitus, con el fin de contribuir a difundir el conocimiento. Materialesy método: tres revisores independientes realizaron la búsqueda en distintas bases de datos entre ellas Pubmed y ScienceDirect, utilizando los términos Metfomin AND Cardiovascular disease AND inflamatory response AND Hyperlipidemia, Biguanides, Diabetes Mellitus, Diabetes complications, Obesity, Vascular diseases AND Cancer; y Metfomina y enfermedad cardiovascular, metformina y cáncer se seleccionaron los artículos desde el año 2010, encontrando 13 828 artículos, de los cuales se incluyeron 144. Conclusión: más allá del control glucémico, la metformina, modifica la “memoria metabólica”, reduce mediadores inflamatorios y el grosor de pared arterial, disminuye factores
trombóticos y reduce la prevalencia de falla cardiaca logrando impactar la morbimortalidad y mediante cambios moleculares o genéticos, tiene potencial uso como anticancerígeno. El clínico debe conocer estos efectos para favorecer su pronto inicio en los casos indicados. MÉD.UIS. 2017;30(1):57-71.

Palabras clave: Metformina. Diabetes Mellitus. Proteínas Quinasas Activada por AMP. Obesidad. Enfermedades Vasculares. Neoplasias.

https://doi.org/10.18273/revmed.v30n1-2017005
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Referencias

Centers for Disease Control and Prevention. National Diabetes

Statistics Report: Estimates of Diabetes and Its Burden in the

United States, 2014. Atlanta, GA: US Department of Health and

Human Services; 2014.

Zhu M, Li J, Li Z, Luo W, Dai D, Weaver SR, et al. Mortality rates

and the causes of death related to diabetes mellitus in Shanghai

Songjiang District: an 11-year retrospective analysis of death

certificates. BMC Endocr Disord. 2015;15:45.

Action to Control Cardiovascular Risk in Diabetes Study G,

Gerstein HC, Miller ME, Byington RP, Goff DC, Jr., Bigger JT, et al.

Effects of intensive glucose lowering in type 2 diabetes. N Engl J

Med. 2008;358(24):2545-59.

Nandy M, Mandal A, Banerjee S, Ray K. A prescription survey

in diabetes assessing metformin use in a tertiary care hospital in

Eastern India. J Pharmacol Pharmacother. 2012;3(3):273-5.

American Diabetes Association. Approaches to Glycemic

Treatment. Diabetes Care. 2016;39:S52-9.

Triggle CR, Ding H. Cardiovascular impact of drugs used in the

treatment of diabetes. Ther Adv Chronic Dis. 2014;5(6):245-68.

American Diabetes Association. Standards of medical care in

diabetes. Diabetes Care. 2014;37:S14-S80.

Konrad K, Datz N, Engelsberger I, Grulich-Henn J, Hoertenhuber

T, Knauth B, et al. Current use of metformin in addition to insulin

in pediatric patients with type 1 diabetes mellitus: an analysis

based on a large diabetes registry in Germany and Austria.

Pediatr Diabetes. 2014: 16(7):529-37

Glueck CJ, Fontaine RN, Wang P, Subbiah MT, Weber K, Illig E,

et al. Metformin reduces weight, centripetal obesity, insulin,

leptin, and low-density lipoprotein cholesterol in nondiabetic,

morbidly obese subjects with body mass index greater than 30.

Metabolism. 2001;50:856-61.

Pratley RE. The early treatment of type 2 diabetes. Am J Med.

;126:S2-9.

Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE.

Metabolic effects of metformin in non-insulin-dependent

diabetes mellitus. N Engl J Med. 1995;333:550-4.

Pernicova I, Korbonits M. Metformin--mode of action and clinical

implications for diabetes and cancer. Nat Rev Endocrinol.

;10(3):143-56.

Ferrannini E. The Target of Metformin in Type 2 Diabetes. N Engl

J Med. 2014;371:1547-8.

Baur JA, Birnbaum MJ. Control of gluconeogenesis by metformin:

does redox trump energy charge? Cell Metab. 2014;20(2):197-9.

Hundal RS, Krssak M, Dufour S, Laurent D, Lebon V,

Chandramouli V, et al. Mechanism by which metformin

reduces glucose production in type 2 diabetes. Diabetes.

;49(12):2063-9.

Rena G, Pearson ER, Sakamoto K. Molecular mechanism of

action of metformin: Old or new insights? Diabetologia.

;56(9):1898-906.

Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli

F. Cellular and molecular mechanisms of metformin: an overview.

Clin Sci. 2011;122(6):253-70.

Wu T, Thazhath SS, Bound MJ, Jones KL, Horowitz M, Rayner

CK. Mechanism of increase in plasma intact GLP-1 by metformin

in type 2 diabetes: Stimulation of GLP-1 secretion or reduction in

plasma DPP-4 activity? Diabetes Res Clin Pract. 2014;106(1):e3-6.

Farilla L, Hui H, Bertolotto C, Kang E, Bulotta A, Di Mario U,

et al. Glucagon-like peptide-1 promotes islet cell growth and

inhibits apoptosis in Zucker diabetic rats. Endocrinology.

;143(11):4397-408.

Lima MM, Balladares N, Torres C, Vera L, Bognanno F, Marin M,

et al. Physiological role of incretins and its importance in type

diabetes mellitus. Infor Med. 2009;11(1):437-43.

Qaseem A, Humphrey LL, Sweet DE, Starkey M, Shekelle P.

Oral pharmacologic treatment of type 2 diabetes mellitus:

A clinical practice guideline from the american college of

physicians. Ann Intern Med. 2012;156(3):218-31.

Bennett WL, Maruthur NM, Singh S, Segal JB, Wilson LM,

Chatterjee R, et al. Comparative effectiveness and safety of

medications for type 2 diabetes: An update including new drugs

and 2-drug combinations. Ann Intern Med. 2011;154(9):602-18.

Ryan DH, Espeland MA, Foster GD, Haffner SM, Hubbard VS,

Johnson KC, et al. Look AHEAD (Action for Health in Diabetes):

design and methods for a clinical trial of weight loss for the

prevention of cardiovascular disease in type 2 diabetes. Control

Clin Trials; 2003;24(5):610-28.

Romanelli RJ, Chung S, Pu J, Nimbal V, Zhao B, Palaniappan L.

Comparative effectiveness of early versus delayed metformin

in the treatment of type 2 diabetes. Diabetes Res Clin Pract.

;108(1):1-9.

Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones

NP, et al. Glycemic durability of rosiglitazone, metformin, or

glyburide monotherapy. N Engl J Med. 2006;355:2427-43.

No authors. Intensive blood-glucose control with sulphonylureas

or insulin compared with conventional treatment and risk

of complications in patients with type 2 diabetes (UKPDS

. UK Prospective Diabetes Study (UKPDS) Group. Lancet.

;352(9131):837-53.

Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S,

et al. Intensive insulin therapy prevents the progression of diabetic

microvascular complications in Japanese patients with noninsulin-

dependent diabetes mellitus: a randomized prospective

-year study. Diabetes Res Clin Pract; 1995;28:103-17.

Scarpello JHB. Improving survival with metformin: the

evidence base today. Diabetes Metab. 2003;29(4):6S36-43.

Held C, Hjemdahl P, Eriksson SV, Bjorkander I, Forslund L,

Rehnqvist N. Prognostic implications of intima-media thickness

and plaques in the carotid and femoral arteries in patients with

stable angina pectoris. Eur Heart J. 2001;22(1):62-72.

Tapp RJ, Shaw JE, Zimmet PZ, Balkau B, Chadban SJ, Tonkin AM,

et al. Albuminuria is evident in the early stages of diabetes onset:

Results from the Australian Diabetes, Obesity, and Lifestyle

Study (AusDiab). Am J Kidney Dis. 2004;44(5):792-8.

Smith AG, Singleton JR. The diagnostic yield of a standardized

approach to idiopathic sensory-predominant neuropathy. Arch

Intern Med. 2004;164(9):1021-5.

Franciosi M, Pellegrini F, Sacco M, De Berardis G, Rossi

MCE, Strippoli GFM, et al. Identifying patients at risk for

microalbuminuria via interaction of the components of the

metabolic syndrome: A cross-sectional analytic study. Clin J Am

Soc Nephrol. 2007;2(5):984-91.

Kim YI, Kim CH, Choi CS, Chung YE, Lee MS, Lee SI, et al.

Microalbuminuria is associated with the insulin resistance

syndrome independent of hypertension and type 2 diabetes in

the Korean population. Diabetes Res Clin Pract. 2001;52(2):145-

Group DPPR. The prevalence of retinopathy in impaired glucose

tolerance and recent-onset diabetes in the Diabetes Prevention

Program. Diabet Med. 2007;24(2):137-44.

Wong TY, Liew G, Tapp RJ, Schmidt MI, Wang JJ, Mitchell P, et al. Relation between fasting glucose and retinopathy for diagnosis of

diabetes: three population-based cross-sectional studies. Lancet.

;371(9614):736-43.

Hu FB, Stampfer MJ, Haffner SM, Solomon CG, Willett WC,

Manson JE. Elevated risk of cardiovascular disease prior to clinical

diagnosis of type 2 diabetes. Diabetes Care. 2002;25(7):1129-34.

Levitzky YS, Pencina MJ, D’Agostino RB, Meigs JB, Murabito

JM, Vasan RS, et al. Impact of Impaired Fasting Glucose on

Cardiovascular Disease. The Framingham Heart Study. J Am Coll

Cardiol. 2008;51(3):264-70.

Barr ELM, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ,

Dunstan DW, et al. Risk of Cardiovascular and All-Cause Mortality

in Individuals With Diabetes Mellitus, Impaired Fasting Glucose,

and Impaired Glucose Tolerance. Circulation. 2007;116(2):151-7.

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin

JM, Walker EA, et al. Reduction in the incidence of type 2

diabetes with lifestyle intervention or metformin. N Engl J Med;

;346(6):393-403

Copeland KC, Silverstein J, Moore KR, Prazar GE, Raymer T,

Shiffman RN, et al. Management of newly diagnosed type 2

Diabetes Mellitus (T2DM) in children and adolescents. Pediatrics.

;131(2):364-82.

Chang RJ, Nakamura RM, Judd HL, Kaplan SA. Insulin resistance

in nonobese patients with polycystic ovarian disease. J Clin

Endocrinol Metab. 1983;57(2):356-9.

Nestler JE. Metformin for the treatment of the polycystic ovary

syndrome. N Engl J Med. 2008;358(1):47-54.

Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial

J. Prevalence of impaired glucose tolerance and diabetes

in women with polycystic ovary syndrome. Diabetes Care.

;22(1):141-6.

Sharma ST, Wickham III EP, Nestler JE. Changes in glucose

tolerance with metformin treatment in polycystic ovary syndrome:

a retrospective analysis. Endocr Pract. 2007;13(4):373-9.

Diabetes Prevention Program Research G. Long-term safety,

tolerability, and weight loss associated with metformin in the

Diabetes Prevention Program Outcomes Study. Diabetes Care.

;35(4):731-7.

Becker S, Dossus L, Kaaks R. Obesity related hyperinsulinaemia

and hyperglycaemia and cancer development. Arch Physiol

Biochem. 2009;115(2):86-96.

Rizvi AA, Nikolic D, Sallam HS, Montalto G, Rizzo M, Abate N.

Adipokines and lipoproteins: modulation by antihyperglycemic

and hypolipidemic agents. Metab Syndr Relat Disord.

;12(1):1-10.

Leblanc ES, O’Connor E, Whitlock EP, Patnode CD, Kapka T.

Effectiveness of primary care-relevant treatments for obesity

in adults: a systematic evidence review for the U.S. Preventive

Services Task Force. Ann Intern Med. 2011;155(7):434-47.

49.Levri KM, Slaymaker E, Last A, Yeh J, Ference J, D’Amico F, et al. Metformin as treatment for overweight and obese adults: a

systematic review. Ann Fam Med. 2005;3(5):457-61.

Nieuwenhuis-Ruifrok AE, Kuchenbecker WK, Hoek A, Middleton

P, Norman RJ. Insulin sensitizing drugs for weight loss in women

of reproductive age who are overweight or obese: systematic

review and meta-analysis. Hum Reprod Update. 2009;15(1):57-68.

Bruno RV, de Avila MA, Neves FB, Nardi AE, Crespo CM,

Sobrinho AT. Comparison of two doses of metformin (2.5 and 1.5

g/day) for the treatment of polycystic ovary syndrome and their

effect on body mass index and waist circumference. Fertil Steril.

;88(2):510-2.

McDonagh MS, Selph S, Ozpinar A, Foley C. Systematic review of

the benefits and risks of metformin in treating obesity in children

aged 18 years and younger. JAMA pediatr. 2014;168(2):178-84.

Khan AY, Macaluso M, McHale RJ, Dahmen MM, Girrens K, Ali

F. The adjunctive use of metformin to treat or prevent atypical

antipsychotic-induced weight gain: a review. J Psychiatr Pract.

;16(5):289-96.

Hasnain M, Fredrickson SK, Vieweg WV. Metformin for obesity and glucose dysregulation in patients with schizophrenia receiving

antipsychotic drugs. J Psychopharmacol. 2011;25(6):715-21.

Unnikrishnan IR, Anjana R, Mohan V. Importance of Controlling

Diabetes Early–The Concept of Metabolic Memory, Legacy Effect

and the Case for Early Insulinisation. J Assoc Physicians India.

;59Supplement:8-12.

Writing Team for the Diabetes C, Complications Trial/

Epidemiology of Diabetes I, Complications Research G. Effect of

intensive therapy on the microvascular complications of type 1

diabetes mellitus. JAMA. 2002;287(19):2563-9.

Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of

intensive blood-glucose control on late complications of type I

diabetes. Lancet. 1993;341(8856):1306-9.

King P, Peacock I, Donnelly R. The UK prospective diabetes

study (UKPDS): clinical and therapeutic implications for type 2

diabetes. Br J Clin Pharmacol. 1999;48(5):643-8.

Barreto-Torres G, Soto Hernandez J, Jang S, Rodriguez-Munoz

AR, Torres-Ramos CA, Basnakian AG, et al. The beneficial effects

of AMP-kinase activation against oxidative stress are associated

with prevention of PPARalpha-cyclophilin D interaction in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2015;308(7):749-58.

Zheng Z, Chen H, Li J, Li T, Zheng B, Zheng Y, et al. Sirtuin

-mediated cellular metabolic memory of high glucose via the

LKB1/AMPK/ROS pathway and therapeutic effects of metformin.

Diabetes. 2012;61(1):217-28.

Ceriello A. La memoria metabólicainducida por la hiperglucemia:

el nuevo reto en la prevención de la enfermedad cardiovascular

en la diabetes. Rev Esp Cardiol. 2008;8(C):12-18.

Peiro C, Romacho T, Azcutia V, Villalobos L, Fernandez E, Bolanos JP, et al. Inflammation, glucose, and vascular cell damage: the role of the pentose phosphate pathway. Cardiovasc Diabetol.

;15(1):82.

Bailey CJ. Metformin: effects on micro and macrovascular

complications in type 2 diabetes. Cardiovasc Drugs Ther.

;22(3):215-24.

Ewart MA, Kennedy S. AMPK and vasculoprotection. Pharmacol

Ther. 2011;131(2):242-53.

Lubos E, Handy DE, Loscalzo J. Role of oxidative stress and nitric

oxide in atherothrombosis. Front Biosci. 2008;13:5323-44.

Ceriello A, Quagliaro L, Catone B, Pascon R, Piazzola M, Bais

B, et al. Role of hyperglycemia in nitrotyrosine postprandial

generation. Diabetes Care. 2002;25(8):1439-43.

Hashiramoto M, Kaku K. Sirtuin 1 as a key player of ‘metabolic

memory’. J Diabetes Investig. 2013;4(1):34-6.

Winder WW, Hardie DG. AMP-activated protein kinase, a

metabolic master switch: possible roles in type 2 diabetes. Am J

Physiol. 1999;277(1 Pt 1):E1-10.

Ceriello A, Ihnat M, Ross K, Sismey A, Green DW, Kaltreider

RC. Evidence for a cellular “memory” of hyperglycemic stress.

Diabetes. 2005;54:218.

Park IH, Um JY, Hong SM, Cho JS, Lee SH, Lee SH, et al.

Metformin reduces TGF-beta1-induced extracellular matrix

production in nasal polyp-derived fibroblasts. Otolaryngol Head

Neck Surg. 2014;150(1):148-53.

Jang AH, Kim YW. Metformin Reduces Inflammation and Lung

Fibrosis in a Bleomycin-Induced Lung Injury Model (LB505). The

FASEB Journal. 2014;28 Supl 1:505.

Matsumoto K, Sera Y, Abe Y, Tominaga T, Yeki Y, Miyake S.

Metformin attenuates progression of carotid arterial wall

thickness in patients with type 2 diabetes. Diabetes Res Clin

Pract. 2004;64(3):225-8.

Katakami N, Yamasaki Y, Hayaishi-Okano R, Ohtoshi K,

Kaneto H, Matsuhisa M, et al. Metformin or gliclazide, rather

than glibenclamide, attenuate progression of carotid intimamedia

thickness in subjects with type 2 diabetes. Diabetologia.

;47(11):1906-13.

Li L, Mamputu JC, Wiernsperger N, Renier G. Signaling pathways

involved in human vascular smooth muscle cell proliferation

and matrix metalloproteinase-2 expression induced by leptin:

inhibitory effect of metformin. Diabetes. 2005;54(7):2227-34.

Takahashi N, Shibata R, Ouchi N, Sugimoto M, Murohara

T, Komori K. Metformin stimulates ischemia-induced

revascularization through an eNOS dependent pathway in the

ischemic hindlimb mice model. J Vasc Surg. 2015;61(2):489-96.

de Jager J, Kooy A, Schalkwijk C, van der Kolk J, Lehert P, Bets

D, et al. Long-term effects of metformin on endothelial function

in type 2 diabetes: a randomized controlled trial. J Intern Med.

;275(1):59-70.

Pitocco D, Zaccardi F, Tarzia P, Milo M, Scavone G, Rizzo P, et

al. Metformin improves endothelial function in type 1 diabetic

subjects: a pilot, placebo-controlled randomized study. Diabetes

Obes Metab. 2013;15(5):427-31.

Tousoulis D, Koniari K, Antoniades C, Miliou A, Noutsou M,

Nikolopoulou A, et al. Impact of 6 weeks of treatment with

low-dose metformin and atorvastatin on glucose-induced

changes of endothelial function in adults with newly diagnosed

type 2 diabetes mellitus: A single-blind study. Clin Ther.

;32(10):1720-8.

Zhang TX, Xu JX, Peng F, Chai DJ, Lin JX. Metformin reduces

vascular endothelial dysfunction caused by an acute glucose load

in patients with hypertension. Blood Press. 2013;22(2):106-13.

El Messaoudi S, Schreuder TH, Kengen RD, Rongen GA, van

den Broek PH, Thijssen DH, et al. Impact of metformin on

endothelial ischemia-reperfusion injury in humans in vivo: a

prospective randomized open, blinded-endpoint study. PLOS

ONE. 2014;9(4):e96062.

Cantoria MJ, Boros LG, Meuillet EJ. Contextual inhibition of fatty

acid synthesis by metformin involves glucose-derived acetyl-

CoA and cholesterol in pancreatic tumor cells. Metabolomics.

;10(1):91-104.

Geerling JJ, Boon MR, van der Zon GC, van den Berg SA, van

den Hoek AM, Lombes M, et al. Metformin lowers plasma

triglycerides by promoting VLDL-triglyceride clearance by brown

adipose tissue in mice. Diabetes. 2014;63(3):880-91.

Barnea M, Cohen-Yogev T, Chapnik N, Madar Z, Froy O. Effect of

metformin and lipid emulsion on the circadian gene expression

in muscle cells. Int J Biochem Cell Biol. 2014;53(1):151-61.

Yvan-Charvet L, Wang N, Tall AR. Role of HDL, ABCA1, and

ABCG1 transporters in cholesterol efflux and immune responses.

Arterioscler Thromb Vasc Biol. 2010;30(2):139-43.

Li D, Zhang Y, Ma J, Ling W, Xia M. Adenosine monophosphate

activated protein kinase regulates ABCG1-mediated

oxysterol efflux from endothelial cells and protects against

hypercholesterolemia-induced endothelial dysfunction.

Arterioscler Thromb Vasc Biol. 2010;30(7):1354-62.

Pentikainen PJ, Voutilainen E, Aro A, Uusitupa M, Penttila

I, Vapaatalo H. Cholesterol lowering effect of metformin in

combined hyperlipidemia: placebo controlled double blind trial.

Ann Med. 1990;22(5):307-12.

Diehl LA, Fabris BA, Barbosa DS, De Faria EC, Wiechmann

SL, Carrilho AJ. Metformin increases HDL3-cholesterol and

decreases subcutaneous truncal fat in nondiabetic patients

with HIV-associated lipodystrophy. AIDS Patient Care STDS.

;22(10):779-86.

Cittadini A, Napoli R, Monti MG, Rea D, Longobardi S, Netti

PA, et al. Metformin prevents the development of chronic heart

failure in the SHHF rat model. Diabetes. 2012;61(4):944-53.

Evans JM, Ogston SA, Emslie-Smith A, Morris AD. Risk of

mortality and adverse cardiovascular outcomes in type 2

diabetes: a comparison of patients treated with sulfonylureas

and metformin. Diabetologia. 2006;49(5):930-6.

Nichols GA, Gullion CM, Koro CE, Ephross SA, Brown JB. The

incidence of congestive heart failure in type 2 diabetes: an

update. Diabetes Care. 2004;27(8):1879-84

Nichols GA, Koro CE, Gullion CM, Ephross SA, Brown JB. The

incidence of congestive heart failure associated with antidiabetic

therapies. Diabetes Metab Res Rev. 2005 Feb;21(1):51-7.

Rosiak M, Postula M, Kaplon-Cieslicka A, Trzepla E, Czlonkowski

A, Filipiak KJ, et al. Metformin treatment may be associated with

decreased levels of NT-proBNP in patients with type 2 diabetes.

Adv Med Sci. 2013 Dec;58(2):362-8.

Yin M, van der Horst IC, van Melle JP, Qian C, van Gilst WH,

Sillje HH, et al. Metformin improves cardiac function in a

nondiabetic rat model of post-MI heart failure. Am J Physiol

Heart Circ Physiol. 2011 Aug;301(2):H459-68.

Whittington HJ, Hall AR, McLaughlin CP, Hausenloy DJ,

Yellon DM, Mocanu MM. Chronic metformin associated

cardioprotection against infarction: not just a glucose lowering

phenomenon. Cardiovasc Drugs Ther. 2013 Feb;27(1):5-16.

Calvert JW, Gundewar S, Jha S, Greer JJ, Bestermann WH, Tian R, et al. Acute metformin therapy confers cardioprotection against

myocardial infarction via AMPK-eNOS-mediated signaling.

Diabetes. 2008 Mar;57(3):696-705.

Elmadhun NY, Sabe AA, Lassaletta AD, Chu LM, Sellke FW.

Metformin mitigates apoptosis in ischemic myocardium. J Surg

Res. 2014 Nov;192(1):50-8.

Lexis CP, van der Horst IC, Lipsic E, Wieringa WG, de Boer RA,

van den Heuvel AF, et al. Effect of metformin on left ventricular

function after acute myocardial infarction in patients without

diabetes: the GIPS-III randomized clinical trial. JAMA. 2014

Apr;311(15):1526-35.

Li J, Xu JP, Zhao XZ, Sun XJ, Xu ZW, Song SJ. Protective effect of metformin on myocardial injury in metabolic syndrome patients

following percutaneous coronary intervention. Cardiology. 2014 Jan;127(2):133-9.

Calvert JW. Treating percutaneous coronary interventionrelated

myocardial injury with metformin. Cardiology. 2014 Jan;127(2):130-2.

Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur

SM, Habel LA, et al. Diabetes and cancer: a consensus report.

Diabetes Care. 2010 Jul;33(7):1674-85.

Barone BB, Yeh HC, Snyder CF, Peairs KS, Stein KB, Derr RL, et al. Long-term all-cause mortality in cancer patients with preexisting

diabetes mellitus: a systematic review and meta-analysis. JAMA.

Dec;300(23):2754-64.

Kaaks R, Johnson T, Tikk K, Sookthai D, Tjonneland A, Roswall

N, et al. Insulin-like growth factor I and risk of breast cancer by

age and hormone receptor status-A prospective study within the

EPIC cohort. Int J Cancer. 2014 Jun;134(11):2683-90.

Krett NL, Heaton JH, Gelehrter TD. Mediation of insulinlike

growth factor actions by the insulin receptor in H-35 rat

hepatoma cells. Endocrinology. 1987 Jan;120(1):401-8.

Warburg O. On the origin of cancer cells. Science. 1956

Feb;123(3191):309-14.

Jalving M, Gietema JA, Lefrandt JD, de Jong S, Reyners AK, Gans RO, et al. Metformin: taking away the candy for cancer? Eur J

Cancer. 2010 Sep;46(13):2369-80.

Gallagher EJ, LeRoith D. Diabetes, cancer, and metformin:

connections of metabolism and cell proliferation. Ann N Y Acad

Sci. 2011 Dec;1243:54-68.

Bowker SL, Yasui Y, Veugelers P, Johnson JA. Glucoselowering

agents and cancer mortality rates in type 2 diabetes:

assessing effects of time-varying exposure. Diabetologia. 2010

Aug;53(8):1631-7.

Colhoun HM, Group SE. Use of insulin glargine and cancer

incidence in Scotland: a study from the Scottish Diabetes

Research Network Epidemiology Group. Diabetologia. 2009

Sep;52(9):1755-65.

Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering

therapies on cancer risk in type 2 diabetes. Diabetologia. 2009

Sep;52(9):1766-77.

Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans

JM. New users of metformin are at low risk of incident cancer: a

cohort study among people with type 2 diabetes. Diabetes Care.

Sep;32(9):1620-5.

Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris

AD. Metformin and reduced risk of cancer in diabetic patients.

BMJ. 2005;330(7503):1304-5.

Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini

F, Nicolucci A. Metformin therapy and risk of cancer in

patients with type 2 diabetes: systematic review. PLoS One.

;8(8):e71583.

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(5):1092-9.

Del Barco S, Vazquez-Martin A, Cufi S, Oliveras-Ferraros

C, Bosch-Barrera J, Joven J, et al. Metformin: multi-faceted

protection against cancer. Oncotarget. 2011;2(12):896-917.

Shaw RJ. LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta Physiol (Oxf). 2009;196(1):65-80.

Huang X, Wullschleger S, Shpiro N, McGuire VA, Sakamoto K,

Woods YL, et al. Important role of the LKB1-AMPK pathway in

suppressing tumorigenesis in PTEN-deficient mice. Biochem J.

;412(2):211-21.

Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N.

Metformin inhibits mammalian target of rapamycin-dependent

translation initiation in breast cancer cells. Cancer Res.

;67(22):10804-12.

Esfahanian N, Shakiba Y, Nikbin B, Soraya H, Maleki-Dizaji N,

Ghazi-Khansari M, et al. Effect of metformin on the proliferation,

migration, and MMP-2 and -9 expression of human umbilical

vein endothelial cells. Mol Med Rep. 2012;5(4):1068-74.

Rattan R, Ali Fehmi R, Munkarah A. Metformin: an emerging new therapeutic option for targeting cancer stem cells and metastasis. J Oncol. 2012;2012:928127.

Xavier DO, Amaral LS, Gomes MA, Rocha MA, Campos PR, Cota

BD, et al. Metformin inhibits inflammatory angiogenesis in a murine sponge model. Biomed Pharmacother. 2010;64(3):220-5.

Ersoy C, Kiyici S, Budak F, Oral B, Guclu M, Duran C, et al. The

effect of metformin treatment on VEGF and PAI-1 levels in obese

type 2 diabetic patients. Diabetes Res Clin Pract. 2008;81(1):56-60.

Barriere G, Tartary M, Rigaud M. Metformin: a rising star to fight the epithelial mesenchymal transition in oncology. Anticancer

Agents Med Chem. 2013;13(2):333-40.

Cufi S, Vazquez-Martin A, Oliveras-Ferraros C, Martin-Castillo

B, Joven J, Menendez JA. Metformin against TGFbeta-induced

epithelial-to-mesenchymal transition (EMT): from cancer stem

cells to aging-associated fibrosis. Cell cycle. 2010;9(22):4461-8.

Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti

P, Auberger P, et al. The antidiabetic drug metformin exerts an

antitumoral effect in vitro and in vivo through a decrease of

cyclin D1 level. Oncogene. 2008;27(25):3576-86.

Ben Sahra I, Regazzetti C, Robert G, Laurent K, Le Marchand-

Brustel Y, Auberger P, et al. Metformin, independent of AMPK,

induces mTOR inhibition and cell-cycle arrest through REDD1.

Cancer Res. 2011;71(13):4366-72.

Zhuang Y, Miskimins WK. Cell cycle arrest in Metformin treated

breast cancer cells involves activation of AMPK, downregulation

of cyclin D1, and requires p27Kip1 or p21Cip1. J Mol Signal.

;3:18.

Isakovic A, Harhaji L, Stevanovic D, Markovic Z, Sumarac-

Dumanovic M, Starcevic V, et al. Dual antiglioma action of

metformin: cell cycle arrest and mitochondria-dependent

apoptosis. Cell Mol Life Sci. 2007;64(10):1290-302.

Liu B, Fan Z, Edgerton SM, Deng XS, Alimova IN, Lind SE, et al.

Metformin induces unique biological and molecular responses in

triple negative breast cancer cells. Cell cycle. 2009;8(13):2031-40.

Eikawa S, Nishida M, Mizukami S, Yamazaki C, Nakayama E,

Udono H. Immune-mediated antitumor effect by type 2 diabetes

drug, metformin. Proc Natl Acad Sci U.S.A. 2015;112(6):1809-14.

Goodwin PJ, Stambolic V. Obesity and insulin resistance in breast cancer--chemoprevention strategies with a focus on metformin. Breast. 2011;20(Suppl 3):S31-5.

Qu C, Zhang W, Zheng G, Zhang Z, Yin J, He Z. Metformin

reverses multidrug resistance and epithelial-mesenchymal

transition (EMT) via activating AMP-activated protein kinase

(AMPK) in human breast cancer cells. Mol Cell Biochem. 2014;386(1-2):63-71.

Iliopoulos D, Hirsch HA, Struhl K. Metformin decreases the

dose of chemotherapy for prolonging tumor remission in mouse

xenografts involving multiple cancer cell types. Cancer Res.

;71(9):3196-201.

Kim J, Lim W, Kim EK, Kim MK, Paik NS, Jeong SS, et al. Phase

II randomized trial of neoadjuvant metformin plus letrozole

versus placebo plus letrozole for estrogen receptor positive

postmenopausal breast cancer (METEOR). BMC Cancer.

Rocha GZ, Dias MM, Ropelle ER, Osorio-Costa F, Rossato FA,

Vercesi AE, et al. Metformin amplifies chemotherapy-induced

AMPK activation and antitumoral growth. Clin Cancer Res.

;17(12):3993-4005.

Hwang IC, Park SM, Shin D, Ahn HY, Rieken M, Shariat SF.

Metformin Association with Lower Prostate Cancer Recurrence

in Type 2 Diabetes: a Systematic Review and Meta-analysis.

Asian Pac J Cancer Prev. 2015;16(2):595-600.

Raval AD, Thakker D, Vyas A, Salkini M, Madhavan S,

Sambamoorthi U. Impact of metformin on clinical outcomes

among men with prostate cancer: a systematic review and metaanalysis. Prostate Cancer Prostatic Dis. 2015;18:110-21.

Yu H, Yin L, Jiang X, Sun X, Wu J, Tian H, et al. Effect of

metformin on cancer risk and treatment outcome of prostate

cancer: a meta-analysis of epidemiological observational studies.

PLoS One. 2014;9(12):e116327.

Col NF, Ochs L, Springmann V, Aragaki AK, Chlebowski RT.

Metformin and breast cancer risk: a meta-analysis and critical

literature review. Breast Cancer Res Treat. 2012;135(3):639-46.

Rego DF, Pavan LM, Elias ST, De Luca Canto G, Guerra EN.

Effects of metformin on head and neck cancer: A systematic

review. Oral Oncol. 2015;51(5):416-22.

Sakoda LC, Ferrara A, Achacoso NS, Peng T, Ehrlich SF,

Quesenberry CP, Jr., et al. Metformin use and lung cancer

risk in patients with diabetes. Cancer Prev Res (Phila). 2015;8(2):174-9.

Zhang ZJ, Bi Y, Li S, Zhang Q, Zhao G, Guo Y, et al. Reduced

risk of lung cancer with metformin therapy in diabetic patients:

a systematic review and meta-analysis. Am J Epidemiol.

;180(1):11-4.

Wang Z, Lai ST, Xie L, Zhao JD, Ma NY, Zhu J, et al. Metformin

is associated with reduced risk of pancreatic cancer in patients

with type 2 diabetes mellitus: a systematic review and metaanalysis.

Diabetes Res Clin Pract. 2014;106(1):19-26.

Pinilla AE. Construcción y evaluación de un perfil de

competencias profesionales en medicina interna. Colección

Desarrollo Humano. Bogotá: Editorial Universidad Nacional de

Colombia; 2015.

Patiño JF. Humanismo, medicina y ciencia. En: Silva G (Ed.).

Colección Obra Selecta. Bogotá: Editorial Universidad Nacional

de Colombia; 2011.

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