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Vol. 55. Issue S2.
Guía de actualización en el tratamiento de la diabetes tipo 2 y sus complicaciones
Pages 39-52 (March 2008)
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Vol. 55. Issue S2.
Guía de actualización en el tratamiento de la diabetes tipo 2 y sus complicaciones
Pages 39-52 (March 2008)
Guía de actualización en el tratamiento de la diabetes tipo 2 y sus complicaciones
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Metformina
Metformin
Visits
26104
A. Soto, M.J. Iglesias, M. Buño, D. Bellido
Corresponding author
diego_bellido@arrakis.es

Correspondencia: Dr. D. Bellido Guerrero. Hospital, 29-31, 4.° A. 15401 Ferrol. La Coruña. España.
Servicio de Endocrinología y Nutrición. Complejo Hospitalario Juan Canalejo. La Coruña. España
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La metformina, la única biguanida actualmente comercializada, es más que un hipoglucemiante oral, un fármaco glucorregulador. Los aspectos moleculares de su mecanismo de acción no se conocen completamente, pero su acción fundamental se basa en el incremento de la sensibilidad hepática a la insulina y la facilitación del transporte de glucosa en situaciones de hiperglucemia y resistencia a la insulina. En la actualidad, se considera el fármaco de elección en el tratamiento inicial en pacientes con diabetes mellitus tipo 2, con y sin exceso de peso. Su utilización en tratamiento combinado con antidiabéticos orales (sulfonilureas, meglitinidas, glitazonas, inhibidores de las alfaglucosidasas) e insulina mejora su perfil terapéutico. Su efecto positivo en el control de la glucemia se ve complementado en su uso clínico por otras acciones, y evita la ganancia de peso corporal, y la mejoría de perfil lipídico y de riesgo cardiometabólico. La metformina ha demostrado eficacia en estudios de prevención de diabetes mellitus y en otras indicaciones asociadas a la resistencia a la insulina.

Palabras clave:
Metformina
Diabetes mellitus tipo 2
Insulinorresistencia
Biguanidas

Metformin, the only biguanide currently available commercially, is more than an oral hypoglycemic agent, it is also a glycoregulatory drug. The molecular features of its mechanism of action are not well defined, but its main action is based on an increase of insulin sensitivity in the liver and on facilitating glucose transport in situations of hyperglycemia and insulin resistance. Metformin is currently the initial drug of choice in patients with type 2 diabetes mellitus with and without excess weight. Its use in combination with oral antidiabetic agents (sulfonylureas, meglitinides, glitazones, alpha-glucosidase inhibitors) and insulin improve its therapeutic profile. Clinically, its positive effect on glycemic control is complemented by other actions such as avoidance of weight gain and improvement of lipid and cardiometabolic risk. The efficacy of metformin has been demonstrated in studies of diabetes mellitus prevention and other indications associated with insulin resistance.

Key words:
Metformin
Type 2 diabetes mellitus
Insulin resistance
Biguanides
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Bibliografía
[1.]
C.J. Bailey.
Biguanides and NIDDM.
Diabetes Care, 15 (1992), pp. 755-772
[2.]
C.J. Bailey, R.C. Turner.
Drug therapy: metformin.
N Engl J Med, 334 (1996), pp. 574-579
[3.]
A.J. Krentz, R.E. Ferner, C.J. Bailey.
Comparative tolerability profiles of oral antidiabetic agents.
Drug Saf, 11 (1994), pp. 223-241
[4.]
I.W. Campbell, H.C.S. Howlett.
Worldwide experience of metformin as an effective glucose-lowering agent: a metaanalysis.
Diabetes Metab Rev, 11 (1995), pp. S57-S62
[5.]
R.A. DeFronzo, A.M. Goodman.
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus.
N Engl J Med, 333 (1995), pp. 541-548
[6.]
UK Prospective Diabetes Study Group.
UK Prospective Diabetes Study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease.
Diabetes, 44 (1995), pp. 1249-1258
[7.]
C.J. Bailey.
Metformin – an update.
Gen Pharmacol, 24 (1993), pp. 1299-1309
[8.]
N.F. Wiernsperger.
Preclinical pharmacology of biguanides.
Handbook of Experimental Pharmacology, 119 (1996), pp. 305-358
[9.]
S.E. Inzucchi.
Metformin or thiazolidinediones as first-line therapy for type 2 diabetes: focus on cardiovascular protection.
Pract Diabetol, 21 (2002), pp. 7-12
[10.]
L.A. Stadtmauer, B.C. Wong, S. Oehninger.
Should patients with metforpolycystic ovary syndrome be treated with metformin? Bene-comfits of insulin sensitizing drugs in polycystic ovary syndrome: beyond ovulation induction.
Hum Reprod, 17 (2002), pp. 3016-3026
[11.]
G. Cohn, G. Valdes, D.M. Capuzzi.
Pathophysiology and treatment of the dyslipidemia of insulin resistance.
Curr Cardiol Rep, 3 (2001), pp. 416-423
[12.]
H. Mehnert.
Metformin, the rebirth of a biguanide: mechanism of action and place in the prevention and treatment of insulin resistance.
Exp Clin Endocrinol Diab, 109 (2001), pp. S259-S264
[13.]
D. Kirpichnikov, S.I. McFarlane, J.R. Sowers.
Metformin: an update.
Ann Intern Med, 137 (2002), pp. 25-33
[14.]
K. Cusi, R.A. DeFronzo.
Metformin: a review of its metabolic effects.
Diabetes Rev, 6 (1998), pp. 89-131
[15.]
G. Zhou, R. Myers, Y. Li, Y. Chen, X. Shen, J. Fenyk-Melody, et al.
Role of AMP-activated protein kinase in the mechanism of action of metformin.
J Clin Invest, 108 (2001), pp. 1167-1174
[16.]
W.W. Winder, D.G. Hardie.
AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes.
Am J Physiol, 277 (1999), pp. E1-E10
[17.]
C.Y. Jeng, W.H. Sheu, M.M. Fuh, Y.D. Chen, G.M. Reaven.
Relationship between hepatic glucose production and fasting plasma glucose concentration in patients with NIDDM.
Diabetes, 43 (1994), pp. 1440-1444
[18.]
J. Radziuk, Z. Zhang, N. Wiernsperger, S. Pye.
Effects of metformin on lactate uptake and gluconeogenesis in the perfused rat liver.
Diabetes, 46 (1997), pp. 1406-1413
[19.]
D.E. Cook, J.B. Blair, C. Gilfillan, H.A. Lardy.
Mode of action of hypoglycaemic agents. IV. Control of the hypoglycaemic activity of phenethylbiguanide in rats and guinea pigs.
Biochem Pharmacol, 22 (1973), pp. 2121-2128
[20.]
N. Wollen, C.J. Bailey.
Inhibition of hepatic gluconeogenesis by metformin. Synergism with insulin.
Biochem Pharmacol, 37 (1988), pp. 4353-4358
[21.]
N. Wollen, C.J. Bailey.
Metformin potentiates the antigluconeogenic action of insulin.
Diabete Metab, 14 (1988), pp. 88-91
[22.]
B. Yu, S. Pugazhenthi, R.L. Khandelwal.
Effects of metformin on glucose and glucagon regulated gluconeogenesis in cultured normal and diabetic hepatocytes.
Biochem Pharmacol, 48 (1994), pp. 949-954
[23.]
F. Alengrin, G. Grossi, B. Canivet, J. Dolais-Kitabgi.
Inhibitory effects of metformin on insulin and glucagon action in rat hepatocytes involve post-receptor alterations.
Diabete Metab, 13 (1987), pp. 591-597
[24.]
T. Komori, N. Hotta, M. Kobayashi, F. Sakakibara, N. Koh, N. Sakamoto.
Biguanides may produce hypoglycemic action in isolated rat hepatocytes through their effects on L-alanine transport.
Diabetes Res Clin Pract, 22 (1993), pp. 11-17
[25.]
D. Argaud, H. Roth, N. Wiernsperger, X.M. Leverve.
Metformin decreases gluconeogenesis by enhancing the pyruvate kinase flux in isolated rat hepatocytes.
Eur J Biochem, 213 (1993), pp. 1341-1348
[26.]
D. Gawler, G. Milligan, M.D. Houslay.
Treatment of streptozotocin-diabetic rats with metformin restores the ability of insulin to inhibit adenylate cyclase activity and demonstrates that insulin does not exert this action through the inhibitory guanine nucleotide regulatory protein Gi.
Biochem J, 249 (1988), pp. 537-542
[27.]
D.J. Gawler, A. Wilson, M.D. Houslay.
Metformin treatment of lean and obese Zucker rats modulates the ability of glucagons and insulin to regulate hepatocyte adenylate cyclase activity.
J Endocrinol, 122 (1989), pp. 207-212
[28.]
B. Melin, G. Cherqui, M.J. Blivet, M. Caron, O. Lascols, J. Capeau, et al.
Dual effect of metformin in cultured rat hepatocytes: potentiation of insulin action and prevention of insulin-induced resistance.
Metabolism, 39 (1990), pp. 1089-1095
[29.]
C. Minassian, S. Tarpin, G. Mithieux.
Role of glucose-6-phosphatase, glucokinase and glucose-6-phosphate in liver insulin resistance and its correction by metformin.
Biochem Pharmacol, 55 (1998), pp. 1213-1219
[30.]
S. Saleh, A. Abdel-Khalek, M.T. Khayyal, A.M. Masri, A.A. Sharat.
Studies of the effect of oral hypoglycaemic agents on hepatic glycogenolysis.
Pharmacol Res Commun, 6 (1974), pp. 539-550
[31.]
J.S. Pears, R.T. Jung, A. Burchell.
Contrasting effects of metformin on glucose-6-phosphatase from fed and diabetic livers [abstract].
Diabetic Med, 7 (1990), pp. 12
[32.]
R.G. Yoa, J.R. Rapin, N.F. Wiernsperger, A. Martinand, I. Belleville.
Demonstration of defective glucose uptake and storage in erythrocytes from non-insulin dependent diabetic patients and effects of metformin.
Clin Exp Pharmacol Physiol, 20 (1993), pp. 563-567
[33.]
A.J. Scheen.
Clinical pharmacokinetics of metformin.
Clin Pharmacokinet, 30 (1996), pp. 359-371
[34.]
L. Rossetti, R.A. DeFronzo, R. Gherzi, P. Stein, G. Andraghetti, G. Falzetti, et al.
Effect of metformin treatment on insulin action in diabetic rats: in vivo and in vitro correlations.
Metabolism, 39 (1990), pp. 425-435
[35.]
C.J. Bailey, K.J. Mynett, T. Page.
Importance of the intestine as a site of metformin-stimulated glucose utilization.
Br J Pharmacol, 112 (1994), pp. 671-675
[36.]
C.J. Bailey, J.A. Puah.
Effect of metformin on glucose metabolism in mouse soleus muscle.
Diabetes Metab, 12 (1986), pp. 212-218
[37.]
P. Damsbo, A. Handbery, H. Beck-Nielsen.
Reversibility of the defect in glycogen synthase activity in skeletal muscle from obese NIDDs treated with diet and metformin [abstract 1070].
Diabetes, 39 (1990), pp. 277
[38.]
M. Cigolini, O. Bosello, C. Zancanaro, P.G. Orlandi, O. Fezzi, U. Smith.
Influence of metformin on metabolic effect of insulin in human adipose tissue in vitro.
Diabete Metab, 10 (1984), pp. 311-315
[39.]
F. Abbasi, M. Carantoni, Y.D. Chen, G.M. Reaven.
Further evidence for a central role of adipose tissue in the antihyperglycemic effect of metformin.
Diabetes Care, 21 (1998), pp. 1301-1305
[40.]
S. Muntoni.
Inhibition of fatty acid oxidation by biguanides: implications for metabolic physiopathology.
Adv Lipid Res, 12 (1974), pp. 311-377
[41.]
A. Riccio, S. Del Prato, S. Vigili de Kreutzenberg, A. Tiengo.
Glucosa and lipid metabolism in non-insulin-dependent diabetes. Effect of metformin.
Diabetes Metab, 17 (1991), pp. 180-184
[42.]
G. Perriello, P. Misericordia, E. Volpi, A. Santucci, C. Santucci, E. Ferrannini, et al.
Acute antihyperglycemic mechanisms of metformin in NIDDM. Evidence for suppression of lipid oxidation and hepatic glucose production.
Diabetes, 43 (1994), pp. 920-928
[43.]
I. Zavaroni, E. Dall’Aglio, F. Bruschi, O. Alpi, C. Coscelli, U. Butturini.
Inhibition of carbohydrate induced hypertriglyceridemia by metformin.
Horm Metab Res, 16 (1984), pp. 85-87
[44.]
J. Jeppesen, M.Y. Zhou, Y.D. Chen, G.M. Reaven.
Effect of metformin on postprandial lipemia in patients with fairly to poorly controlled NIDDM.
Diabetes Care, 17 (1994), pp. 1093-1099
[45.]
L.H. Storlien, L.A. Baur, A.D. Kriketos, D.A. Pan, G.J. Cooney, A.B. Jenkins, et al.
Dietary fats and insulin action.
Diabetologia, 39 (1996), pp. 621-631
[46.]
G. Boden.
Role of fatty acids in the pathogenesis of insulin resistance and NIDDM.
Diabetes, 46 (1997), pp. 3-10
[47.]
L. Penicaud, Y. Hitier, P. Ferre, J. Girard.
Hypoglycaemic effect of metformin in genetically obese (fa/fa) rats results from an increased utilization of blood glucose by intestine.
Biochem J, 262 (1989), pp. 881-885
[48.]
C.J. Bailey, C. Wilcock, C. Day.
Effect of metformin on glucose metabolism in the splanchnic bed.
Br J Pharmacol, 105 (1992), pp. 1009-1013
[49.]
R.G. Yoa, J.R. Rapin, N.F. Wiernsperger, A. Martinand, I. Belleville.
Demonstration of defective glucose uptake and storage in erythrocytes from non-insulin dependent diabetic patients and effects of metformin.
Clin Exp Pharmacol Physiol, 20 (1993), pp. 563-567
[50.]
A. Godoy.
Epidemiología de la diabetes mellitus y sus complicaciones no coronarias.
Rev Esp Cardiol, 55 (2002), pp. 657-670
[51.]
B. Richter, M. Berger, K. Bergerhoff, C. Clar, A. De Leiva, P. Manning, Cochrane Metabolic and Endocrine Disorders Group, et al.
The Cochrane Library, Issue 3.
Update Software, (2001),
[52.]
P. Gaede, P. Vedel, N. Larsen, G.V. Jensen, H.H. Parving, O. Pedersen.
Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.
N Engl J Med, 348 (2003), pp. 383-393
[53.]
P.H. Gaede, P.V. Jepsen, J.N. Larsen, G.V. Jensen, H.H. Parving, O.B. Pedersen.
The Steno-2 study. Intensive multifactorial intervention reduces the occurrence of cardiovascular disease in patients with type 2 diabetes.
Ugeskr Laeger, 165 (2003), pp. 2658-2661
[54.]
United Kingdom Prospective Diabetes Study Group.
Intesive blood-glucose control with sulfonilureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).
Lancet, 352 (1998), pp. 837-852
[55.]
United Kingdom Prospective Diabetes Study Group.
Effect of Intensive blood-glucose control with merformin on complications in overweight patients with type 2 diabetes (UKPDS 34).
Lancet, 352 (1998), pp. 854-864
[56.]
European Diabetes Policy Group 1998-1999.
A desktop guide to type 2 diabetes mellitus.
Diabet Med, 16 (1999), pp. 716-730
[57.]
Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, et al. Management of hyperglycemia 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. Diabetes Care. 206;29:1963-72.
[58.]
C.R. Ong, L.M. Molyneaux, M.I. Contantino, S.M. Twigg, D.K. Yue.
Longterm efficacy of merformin therapy in nonobese individuals with type 2 diabetes.
Diabetes Care, 29 (2006), pp. 2361-2364
[59.]
L.A. Donnelly, A.SF. Doney, A.T. Hattersley, A.D. Morris, E.R. Pearson.
The effect of obesity on glycaemic response to merformin or sulphonylureas in type 2 diabetes.
Diabet Med, 23 (2006), pp. 128-133
[60.]
IDF Clinical Guidelines Task Force.
Global guideline for type 2 diabetes: recommendations for standard, comprehensive, and minimal care.
Diabet Med, 23 (2006), pp. 579-593
[61.]
A.J. Garber, T.G. Duncan, A.M. Goodman, D.J. Mills, J.L. Rohif.
Efficacy of metformin in type II diabetes: results of a double-blind, placebocontrolled, dose-response trial.
Am J Med, 102 (1997), pp. 491-497
[62.]
R.A. De Fronzo.
Pharmacologic therapy for type 2 diabetes mellitus.
Ann Intern Med, 131 (1999), pp. 281-303
[63.]
J. Jeppesen, M.Y. Zhou, Y.D. Chen, G.M. Reaven.
Effect of metformin on postprandial lipemia in patients with fairly to poorly controlled NIDDM.
Diabetes Care, 17 (1994), pp. 1093-1099
[64.]
I. Grosskopf, Y. Ringel, G. Charach, N. Maharshak, R. Mor, A. Iaina, et al.
Metformin enhances clearance of chylomicrons and chylomicron remnants in nondiabetic mildly overweight glucose-intolerant subjects.
Diabetes Care, 20 (1997), pp. 1598-1602
[65.]
J.A. Johnson, S.H. Simpson, E.L. Toth, S.R. Majumdar.
Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes.
Diabet Med, 22 (2005), pp. 497-502
[66.]
L.S. Hermann, N. Schersten, P.O. Bitzen, T. Kjellstrom, F. Lindgarde, A. Melander.
Therapeutic comparison of metfomin and sulfonylurea, alone and in various combinations.
Diabetes Care, 17 (1994), pp. 1100-1109
[67.]
R.S. Hundal, S.E. Inzucchi.
Metformin: new understandings, new uses.
Drugs, 63 (2003), pp. 1879-1894
[68.]
M. Mata Cases, J. Franch Nadal, A. Goday Arno.
Tratamiento oral con metformina en la diabetes mellitus tipo 2: monoterapia y tratamiento oral combinado.
Med Clin (Barc), 5 (2004), pp. 14-18
[69.]
R. Moses, U. Slobodniuk, S. Boyages, S. Colagiuri, W. Kidson, J. Carter, et al.
Effect of repaglinide addition to merformin monotherapy on glycemic control in patients with type 2 diabetes.
Diabetes Care, 22 (1999), pp. 119-124
[70.]
E.S. Horton, C. Clinkingbeard, M. Gatlin, J. Floey, S. Mallows, S. Shen.
Nateglinide alone and in combination with merfomin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes.
Diabetes Care, 23 (2000), pp. 1660-1665
[71.]
P. Raskin, L. Klaff, J. McGill, S.A. South, P. Hollander, N. Khutoryansky, Repaglinide vs Nateglinide Metfomin Combination Study Group, et al.
Efficacy and safety of combination therapy: ripaglinide plus metformin versus nateglinde plus metformin.
Diabetes Care, 26 (2003), pp. 2063-2068
[72.]
V. Fonseca, J. Rosenstock, R. Patwardhan, A. Salzman.
Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes.
JAMA, 283 (2000), pp. 1695-1702
[73.]
D. Einhorn, M. Rendell, J. Rosenzweig, J.W. Egan, A.L. Mathisen, R.L. Schneider.
Pioglitazone hydrochloride in combination with merformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-cotrolled study. The pioglitazone 027 Study Group.
Clin Ther, 22 (2000), pp. 1395-1409
[74.]
R.R. Holman, R.C. Turner, C.A. Cull, On behalf of the UKPDS Study Group.
A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (UK Prospective Diabetes Study 44).
Diabetes Care, 22 (1999), pp. 960-964
[75.]
J.L. Chiasson, R.G. Joss, J.A. Hunt, C. Palmason, N.W. Rodger, S.A. Ross, et al.
The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled trial.
Ann Intern Med, 121 (1994), pp. 928-935
[76.]
J. Rosenstock, A. Brown, J. Fischer, A. Jain, T. Littlejohn, D. Nadeau, et al.
Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes.
Diabetes Care, 21 (1998), pp. 2050-2055
[77.]
J. Rosenstock, D. Sugimoto, P. Strange, J.A. Stewart, E. Soltes-Rak, G. Dailey.
Triple therapy in type 2 diabetes: insulin glargine or rosiglitazone added to combination therapy of sulfonylurea plus metformin in insulin-naive patients.
Diabetes Care, 29 (2006), pp. 554-559
[78.]
V.L. Roberts, J. Stewart, M. Issa, B. Lake, R. Melis.
Triple therapy with glimepiride in patients with type 2 diabetes mellitus inadequately controlled by metformin and a thiazolidinedione: results of a 30-week, randomized, double-blind, placebo-controlled, parallel-group study.
Clin Ther, 27 (2005), pp. 1535-1547
[79.]
I.B. Hirsch, R.M. Bergenstal, C.G. Parkin, E. Wright, J.B. Buse.
A realworld approach to insulin therapy in primary care practice.
Clin Diabetes, 23 (2005), pp. 78-86
[80.]
H. Yki-Jarvinen, L. Ryysy, K. Nikkila, T. Tolulkas, R. Vanamo, M. Heikkila.
comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomised, controlled trial.
Ann Intern Med, 130 (1999), pp. 389-396
[81.]
K. Cusi, R.A. DeFronzo.
Metformin: areview of its metabolic effects.
Diabetes Reviews, 5 (1998), pp. 89-131
[82.]
Diabetes Prevention Program Research Group.
Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program.
Diabetes Care, 26 (2003), pp. 977-980
[83.]
M. Mata Cases, J. Franch Nadal, A. Godoy Arno.
Tratamiento oral con metformina en la diabetes mellitus tipo 2: monoterapia y tratamiento oral combinado.
Med Clin, 5 (2004), pp. 14-18
[84.]
K.G. Alberti, P.Z. Zimmet.
Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.
Diabetes Med, 15 (1998), pp. 539-553
[85.]
Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group.
Diabetes epidemiology: collaborative analysis of diagnostic criteria in Europe.
Lancet, 354 (1999), pp. 617-621
[86.]
J. Tuomilehto, J. Lindstrom, J.G. Eriksson, T.T. Valle, H. Hamalainen, P. Ilanne-Parikka, Finnish Diabetes Prevention Study Group, et al.
Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.
N Engl J Med, 344 (2001), pp. 1343-1350
[87.]
Diabetes Prevention Program Research Group.
Reduction in the incidence of diabetes with lifestyle intervention or metformin.
N Engl J Med, 346 (2002), pp. 393-403
[88.]
R.S. Hundal, S.E. Inzucchi.
Metformin: new undertandings, new uses.
Drugs, 63 (2003), pp. 1879-1894
[89.]
Y. Wenying, L. Lixiang, Q. Jinwu.
The preventive effect of acarbose and merformin on the IGT population from becoming diabetes mellitus: a 3-year multicentral propsective study.
Chin J Endocrinol Metab, 17 (2001), pp. 131-134
[90.]
J.L. Chiasson, R.G. Josse, R. Gomis, M. Hanefeld, A. Karasik, M. Laakso, For the STOP-NIDDM Trial Research Group.
Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial.
Lancet, 359 (2002), pp. 2072-2077
[91.]
T.A. Buchanan, A.H. Xiang, R.K. Peters, S.L. Kjos, A. Marroquin, J. Goico, et al.
Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women.
Diabetes, 51 (2002), pp. 2796-2803
[92.]
J.S. Torgerson, J. Hauptman, M.N. Boldrin, L. Sjöström.
Xenical in the prevention of diabetes in obese subjects (XENDOS) Study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.
Diabetes Care, 27 (2004), pp. 155-161
[93.]
H.C. Gerstein, S. Yusuf, J. Bosch, J. Pogue, P. Sheridan, N. Dinccag, DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators, et al.
Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial.
Lancet, 23 (2006), pp. 1096-1105
[94.]
R. Padwal, S.R. Majumdar, J.A. Johnson, J. Varney, F.A. McAlister.
A systematic review of drug therapy to delay or prevent type 2 diabetes.
Diabetes Care, 28 (2005), pp. 736-744
[95.]
W. Futterweit.
Polycystic ovary syndrome: clinical perspectivas and management.
Obstet Gynecol Surv, 54 (1999), pp. 403-413
[96.]
A. Dunaif, M. Graf, J. Mandeli, V. Laumas, A. Dobrjansky.
Characterization of groups of hyperandrogenemic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia.
J Clin Endocrinol Metab, 65 (1987), pp. 499-507
[97.]
A. Dunaif, K.R. Segal, W. Futterweit, A. Dobrjansky.
Profound insulin resistance, independent of obesity, in polycystic ovary syndrome.
Diabetes, 38 (1989), pp. 1165-1174
[98.]
J.E. Nestler, D. Stovall, N. Akhter, et al.
Strategies for the use of insulin sensitizing drugs to treat infertility in women with polycystic ovary syndrome.
Fertil Steril, 77 (2002), pp. 209-215
[99.]
M. Pugeat, P.H. Ducluzeau.
Insulin resistance, polycystic ovary syndrome and metformin.
Drugs, 58 (1999), pp. 41-46
[100.]
A. Dunaif.
Insulin resistance and the polycystic ovary syndrome: mechanisms and implications for pathogenesis.
Endocr Rev, 18 (1997), pp. 774-800
[101.]
J.E. Nestler, L.P. Powers, D.W. Matt, K.A. Steingold, S.R. Plymate, R.S. Rittmaster, et al.
A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome.
J Clin Endocrinol Metab, 72 (1991), pp. 83-89
[102.]
M. Costello, B. Shrestha, J. Eden, P. Sjoblom, N. Johnson.
Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome.
Cochrane Database Syst Rev, (2007),
[103.]
C.J. Glueck, H. Phillips, D. Cameron, L. Sieve-Smith, P. Wang.
Continuing metformin throughout pregnancy in women in polycystic ovary syndrome appears to safely reduce first trimester spontaneous abortion: a pilot study.
Fertil Steril, 75 (2001), pp. 46-52
[104.]
D.J. Jakubowicz, M.J. Iuorno, S. Jakubowicz, K.A. Roberts, J.E. Nestler.
Effects of metformin on early pregnancy loss in the polycystic ovary syndrome.
J Clin Endocrinol Metab, 87 (2002), pp. 524-529
[105.]
E.J. Coetzee, W.P.U. Jackson.
Metformin in management of pregnant insulin-independent diabetics.
Diabetologia, 16 (1979), pp. 241-245
[106.]
E.J. Coetzee, W.P. Jackson.
The management of non-insulin dependent diabetes during pregnancy.
Diabetes Res Clin Pract, 1 (1985), pp. 281-287
[107.]
G. Marchesini, M. Brizi, G. Bianchi, S. Tomassetti, M. Zoli, N. Melchionda.
Metformin in non-alcoholic steatohepatitis.
Lancet, 358 (2001), pp. 893-894
[108.]
A. Uygun, A. Kadayifci, A.T. Isik, T. Ozgurtas, S. Deveci, A. Tuzun, et al.
Metformin in the treatment of patients with non-alcoholic steatohepatitis.
Aliment Pharmacol Ther, 19 (2004), pp. 537-544
[109.]
S. Nair, A.M. Diehl, M. Wiseman, G.H. Farr Jr, R.P. Perrillo.
Metformin in the treatment of non-alcoholic steatohepatitis: apilot open label trial.
Aliment Pharmacol Ther, 20 (2004), pp. 23-28
[110.]
S.H. Caldwell, E.E. Hespenheide, J.A. Redick, J.C. Iezzoni, E.H. Battle, B.L. Sheppard.
A pilot study of a thiazolidinedione, troglitazone, in non-alcoholic steatohepatitis.
Am J Gastroenterol, 96 (2001), pp. 519-525
[111.]
B.A. Neuschwander-Tetri, E.M. Brunt, K.R. Wehmeier, D. Oliver, B.R. Bacon.
Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone.
Hepatology, 38 (2003), pp. 1008-1017
[112.]
K. Promrat, G. Lutchman, G.I. Uwaifo, R.J. Freedman, A. Soza, T. Heller, et al.
A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis.
Hepatology, 39 (2004), pp. 188-196
[113.]
E. Bugianesi, E. Gentilcore, R. Manini, S. Natale, E. Vanni, N. Villanova, et al.
A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease.
Am J Gastroenterol, 100 (2005), pp. 1082-1090
[114.]
A.L. Rosenbloom, J.R. Joe, R.S. Young, W.E. Winter.
Emerging epidemia of type 2 diabetes in youth.
Diabetes Care, 22 (1999), pp. 345-354
[115.]
A. Fagot-Campagna.
Emergence of type 2 diabetes mellitus in children: epidemiological evidence.
J Pediatr Endocrinol Metabol, 13 (2000), pp. 1395-1402
[116.]
R. Sinha, G. Fisch, B. Teague, W.V. Tamborlane, B. Banyas, K. Allen, et al.
Prevalence of impaired glucose tolerance among children and adolescents with marked obesity.
N Engl J Med, 346 (2002), pp. 802-810
[117.]
C. Invitti, G. Guzzaloni, L. Gilardini, F. Morabito, G. Viberti.
Prevalence and concomitants of glucose intolerance in European obese children and adolescents.
Diabetes Care, 26 (2003), pp. 118-124
[118.]
D.S. Ludwig, C.B. Ebbeling.
Type 2 diabetes mellitus in children: primary care and public health considerations.
JAMA, 286 (2001), pp. 1427-1430
[119.]
C. Newmark, H. Anhalt.
Type 2 diabetes in children and adolescents.
Pediatr Ann, 362 (2007), pp. 109-113
[120.]
M. Freemark, D. Bursey.
The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes.
Pediatrics, 107 (2001), pp. E55
[121.]
K.L. Jones, S. Arslanian, V.A. Peterokova, J.S. Park, M.J. Tomlinson.
Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial.
Diabetes Care, 25 (2002), pp. 89-94
[122.]
F.J. Palella Jr, K.M. Delaney, A.C. Moorman, M.O. Loveless, J. Fuhrer, G.A. Satten, et al.
Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.
N Engl J Med, 338 (1998), pp. 853-860
[123.]
The CASCADE Collaboration.
Survival after introduction of HAART in people with known duration of HIV-1 infection.
Lancet, 355 (2000), pp. 1158-1159
[124.]
M. Mary-Krause, L. Cotte, A. Simon, M. Partisani, D. Costagliola, The Clinical Epidemiology Group from the French Hospital Database.
Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men.
[125.]
P. Braitstein, B. Yip, K.V. Heath, A.R. Levy, J.S. Montaner, K. Humphries, et al.
Interventional cardiovascular procedures among HIV-infected individuals on antiretroviral therapy 1995-2000.
AIDS, 17 (2003), pp. 2071-2075
[126.]
M. Fantoni, C. Del Borgo, C. Autore.
Evaluation and management of metabolic and coagulative disorders in HIV-infected patients receiving highly active antiretroviral therapy.
AIDS, 17 (2003), pp. S162-S169
[127.]
K. Mulligan, C. Grunfeld, V.W. Tai.
Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection.
J Acquir Immune Defic Syndr, 23 (2000), pp. 35-43
[128.]
M.P. Dube, H. Edmondson-Melancon, D. Qian, R. Aqeel, D. Johnson, T.A. Buchanan.
Prospective evaluation of the effect of initiating indinavir-based therapy on insulin sensitivity and B-cell function in HIV-infected patients.
J AIDS, 27 (2001), pp. 130-134
[129.]
D. Nolan, S. Mallal.
Getting to the HAART of insulin resistance.
AIDS, 15 (2001), pp. 2037-2041
[130.]
H. Murata, P.W. Hruz, M. Mueckler.
Mechanism of insulin resistance caused by HIV protease inhibitor therapy.
J Biol Chem, 275 (2000), pp. 251-254
[131.]
L.A. Nolte, K.E. Yarasheski, F. Kawanaka, J. Fisher, N. Le, J.O. Holloszy.
The HIV protease inhibitor indinavir decreases insulin- and contraction-stimulated glucose transport in skeletal muscle.
Diabetes, 50 (2001), pp. 1397-1401
[132.]
M. Schutt, M. Meier, M. Meyer, J. Klein, S.P. Aries, H.H. Klein.
The HIV-1 protease inhibitor indinavir impairs insulin signalling in HepG2 hepatoma cells.
Diabetologia, 43 (2000), pp. 1145-1148
[133.]
M.P. Dubé.
Disorders of glucose metabolism in patients infected with human immunodeficiency virus.
Clin Infect Dis, 31 (2000), pp. 1467-1475
[134.]
N. Bodasing, R. Fox.
HIV-associated lipodystrophy syndrome: assessment and management.
J Infect, 46 (2003), pp. 87-93
[135.]
S. Grinspoon.
Mechanisms and strategies for insulin resistance in acquired immune deficiency syndrome.
Clin Infect Dis, 37 (2003), pp. S85-S90
[136.]
T. Saint-Marc, J.L. Touraine.
Effects of metformin on insulin resistance and central adiposity in patients receiving effective protease inhibitor therapy.
AIDS, 13 (1999), pp. 1000-1002
[137.]
C. Hadigan, C. Corcoran, N. Basgoz, B. Davis, P. Sax, S. Grinspoon.
Metformin in the treatment of HIV lipodystrophy syndrome: a randomized controlled trial.
JAMA, 284 (2000), pp. 472-477
[138.]
M.C. Gelato, D.C. Mynarcik, J.L. Quick, R.T. Steigbigel, J. Fuhrer, C.E. Brathwaite, et al.
Improved insulin sensitivity and body fat distribution in HIV-infected patients treated with rosiglitazone: a pilot study.
J AIDS, 31 (2002), pp. 163-170
[139.]
J. Sutinen, A.M. Hakkinen, J. Westerbacka, A. Seppala-Lindroos, S. Vehkavaara, J. Halavaara, et al.
Rosiglitazone in the treatment of HAART associated lipodystrophy: a randomized double-blind, placebo-controlled study.
Antiviral Ther, 8 (2003), pp. 199-207
[140.]
J. Tomazic, P. Karner, L. Vidmar, M. Maticic, P.M. Sharma, A. Jane.
Effect of metformin and rosiglitazone on lipid metabolism in HIV infected patients receiving protease inhibitor containing HAART.
Acta Dermatoven, 14 (2005), pp. 99-105
[141.]
E. Martínez, P. Domingo, E. Ribera, A. Milinkovic, J.A. Arroyo, I. Conget, et al.
Effects of metformin or gemfibrozil on the lipodystrophy of HIV-infected patients receiving protease inhibitors.
Antivir Ther, 8 (2003), pp. 403-410
[142.]
C. Hadigan, J.B. Meigs, J. Rabe, R.B. D’Agostino, P.W. Wilson, I. Lipinska, et al.
Framingham Heart Study. Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance.
J Clin Endocrinol Metab, 86 (2001), pp. 939-943
[143.]
J.P. Després, B. Lamarche, P. Mauriège, B. Cantin, G.R. Dagenais, S. Moorjani, et al.
Hyperinsulinemia as an independent risk factor for ischemic heart disease.
N Engl J Med, 334 (1996), pp. 952-957
[144.]
S.M. Haffner.
Epidemiology of insulin resistance and its relation to coronary artery disease.
Am J Cardiol, 84 (1999), pp. 11J-14J
[145.]
S.E. Inzucchi, D.G. Maggs, G.R. Spollett, S.L. Page, F.S. Rife, V. Walton, et al.
Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus.
N Engl J Med, 338 (1998), pp. 867-872
[146.]
R.S. Hundal, M. Krssak, S. Dufour, D. Laurent, V. Lebon, V. Chandramouli, et al.
Mechanism by metformin reduces glucose production in type 2 diabetes.
Diabetes, 49 (2000), pp. 2063-2069
[147.]
K. Cusi, A. Consoli, R.A. DeFronzo.
Metabolic effects of metformin on glucose and lactate metabolism in non insulin-dependent diabetes mellitus.
J Clin Endocrinol Metab, 81 (1996), pp. 4059-4067
[148.]
A. Fontbonne, M.A. Charles, I. Juhan-Vague, J.M. Bard, P. Andre, F. Isnard, et al.
The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution: BIGPRO Study Group.
Diabetes Care, 19 (1996), pp. 920-926
[149.]
C.J. Glueck, P. Wang, R. Fontaine, T. Tracy, L. Sieve-Smith.
Metformin induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with the polycystic ovary syndrome.
Metabolism, 48 (1999), pp. 511-519
[150.]
R. Pasquali, A. Gambineri, D. Biscotti, V. Vicennati, L. Gagliardi, D. Colitta, et al.
Effect of long term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic syndrome.
J Clin Endocrinol Metab, 85 (2000), pp. 2767-2774
[151.]
A. Semplicini, S. Del Prato, M. Giusto, M. Campagnolo, P. Palatini, G.P. Rossi, et al.
Short term effects of metformin on insulin sensitivity and sodium homeostasis in essential hypertensives.
J Hypertens, 11 (1993), pp. S276-S277
[152.]
D.K. Sindelar, C.A. Chu, M. Rohlie, D.W. Neal, L.L. Swift, A.D. Cherrington.
The role of fatty acids in mediating the effects of peripheral insulin on hepatic glucose production in the conscious dog.
Diabetes, 46 (1997), pp. 187-196
[153.]
A. Dresner, D. Laurent, M. Marcucci, M.E. Griffin, S. Dufour, G.W. Cline, et al.
Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylifects 3-kinase activity.
J Clin Invest, 103 (1999), pp. 253-259
[154.]
A.C. Robinson, J. Burke, S. Robinson, D.G. Johnston, R.S. Elkeles.
The effects of metformin on glycemic control and serum lipids in insulin treated NIDDM patients with suboptimal control.
Diabetes Care, 21 (1998), pp. 701-705
[155.]
G.M. Reaven, P. Johnston, C.B. Hollenbeck, R. Skowronski, J.C. Zhang, I.D. Goldfine, et al.
Combined metformin-sulfonylurea treatment of patients with non-insulin dependent diabetes in fair to poor glycemic control.
J Clin Endocrinol Metab, 74 (1992), pp. 1020-1026
[156.]
F. Abbasi, V. Kamath, A.A. Rizvi, M. Carantoni, Y.D. Chen, G.M. Reaven.
Results of a placebo controlled study of the metabolic effects of the addition of metformin to sulfonylurea treated patients: evidence for a central role of adipose tissue.
Diabetes Care, 20 (1997), pp. 1863-1869
[157.]
M.S. Wu, P. Johnston, W.H. Sheu, C.B. Hollenbeck, C.Y. Jeng, I.D. Goldfine, et al.
Effect of metformin on carbohydrate and lipoprotein metabolism in NIDDM patients.
Diabetes Care, 13 (1990), pp. 1-8
[158.]
E.M. Velázquez, S.G. Mendoza, P. Wang, C.J. Gweck.
Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein (a), and immunoreactive insulin levels diabetes among in patients with the polycystic ovary syndrome.
J Pediatr, 46 (1997), pp. 454-457
[159.]
D.S. Bell, F. Ovalle.
Metformin lowers lipoprotein (a) levels.
Diabetes Care, 21 (1998), pp. 2028
[160.]
D.K. Nagi, J.S. Yudkin.
Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects: a study of two ethnic groups.
Diabetes Care, 16 (1993), pp. 621-629
[161.]
M.S. Wu, P. Johnston, W.H. Sheu, C.B. Hollenbeck, C.Y. Jeng, I.D. Goldfine.
Metformin causes a reduction in basal and post-venous occlusion plasminogen inhibitor-1 in type 2 diabetic patients.
Diabet Med, 8 (1991), pp. 361-365
[162.]
M.A. Charles, P. Morange, E. Eschwege, P. Andre, P. Vague, I. Juhan-Vague.
Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese non-diabetic subjects: the BIGPRO study. Biguanides and the prevention of the risk of obesity.
Diabetes Care, 21 (1998), pp. 1967-1972
[163.]
R. Marfella, R. Acampora, G. Verrazzo, P. Ziccardi, N. De Rosa, R. Giunta, et al.
Metformin improves hemodynamic and rheological responses to L-arginine incidence in NIDDM patients.
Diabetes Care, 19 (1996), pp. 934-939
[164.]
C. Desouza, M. Keebler, D.B. McNamara, V. Fonseca.
Drugs affecting homocysteine metabolism.
Drugs, 62 (2002), pp. 605-616
[165.]
J. Vrbikova, M. Bicikova, J. Tallova, M. Hill, L. Starka.
Homocysteine and steroid levels in metformin treated women with polycystic ovary syndrome.
Exp Clin Endocrinol Diabetes, 110 (2002), pp. 74-76
[166.]
E. Ferrannini, G. Buzzigoli, R. Bonadonna, M.A. Giorico, M. Oleggini, L. Graziadei, et al.
Insulin resistance in essential hypertension.
N Engl J Med, 317 (1987), pp. 350-357
[167.]
A.A. Taylor.
Pathophysiology of hypertension and endothelial dysfunction in patients with diabetes.
Endocrinol Metab Clin North Am, 30 (2001), pp. 983-997
[168.]
K. Landin, L. Tengborn, U. Smith.
Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors.
J Intern Med, 229 (1991), pp. 181-187
[169.]
D. Giugliano, A. Quatraro, G. Consoli.
Metformin for obese, insulin treated diabetic patients: improvement in as an independent risk factor for ischemic heart disease.
N J Engl J Med, 334 (1996), pp. 952-957
[170.]
E. Diamanti-Kandarakis, G. Spina, C. Kouli, I. Migdalis.
Increased essential hypertensives endothelial-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy.
J Clin Endocrinol Metab, 86 (2001), pp. 4666-4673
[171.]
P.M. Ridker, R.J. Glyn, C.H. Hennekens.
C-reactive protein adds to the predictive value of total and HDL cholesterol in determing risk of first myocardial infarction.
Circulation, 9 (1998), pp. 2007-2011
[172.]
N.V. Chu, A.P. Kong, D.D. Kim, D. Armstrong, S. Baxi, R. Deutsch, et al.
Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes.
Diabetes Care, 25 (2002), pp. 542-549
[173.]
C.R. Sirtori, C. Pasik.
Re-evaluation of a biguanide, metformin: mechanism of action and tolerability.
Pharmacol Res, 30 (1994), pp. 187-228
[174.]
A.J. Krentz, R.E. Ferner, C.J. Bailey.
Comparative tolerability profiles of oral antidiabetic agents.
Drug Saf, 11 (1994), pp. 223-241
[175.]
M. Stang, D.K. Wysowski, D. Butler-Jones.
Incidence of lactic acidosis in metformin users.
Diabetes Care, 22 (1999), pp. 925-927
[176.]
R.S. Hundal, S.E. Inzucchi.
Metformin. New understandings, new uses.
Drugs, 63 (2003), pp. 1879-1894
[177.]
J.D. Lalau, J.M. Race.
Lactic acidosis in metformin therapy.
Drugs, 58 (1999), pp. 55-60
[178.]
S.R. Salpeter, E. Greyber, G.A. Pasternak, E.E. Salpeter.
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta-analysis.
Arch Intern Med, 163 (2003), pp. 2594-2602
[179.]
Canadian Pharmacist Association.
Compendium of pharmaceuticals and specialties.
The Association, (2001),
[180.]
R.S. Hundal, S.E. Inzucchi.
Metformin. New understandings, new uses.
Drugs, 63 (2003), pp. 1879-1894
[181.]
A.J. Krentz, C.J. Bailey.
Oral antidiabetic agents. Current role in type 2 diabetes mellitus.
Drugs, 65 (2005), pp. 385-411
[182.]
H.C. Howlett, C.J. Bailey.
A risk-benefit assessment of metformin in type 2 diabetes mellitus.
Drug Saf, 20 (1999), pp. 489-503
[183.]
L. Klapholz, E. Leitersdorf, L. Weinrauch.
Leucocytoclastic vasculitis and pneumonitis induced by metformin.
Br Med J (Clin Res Ed), 293 (1986), pp. 483
[184.]
C. Ben Salem, H. Hmouda, R. Slim, M. Denguezli, C. Belajouza, K. Bouraoui.
Rare case of metformin-induced leukocytoclastic vasculitis.
Ann Pharmacother, 40 (2006), pp. 1685-1687
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