Metformin: An old but still the best treatment for type 2 diabetes

Diabetology and Metabolic Syndrome

Volumn 5, Issue 1, 2013, Pages

  Rojas, Lilian Beatriz Aguayo ^a   Gomes, Marilia Brito ^a  

^a STATE UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

Diabetes mellitus; Insulin; Metformin; Resistance

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ACARBOSE; AMILORIDE; CIMETIDINE; DAPAGLIFLOZIN; DIGOXIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLIBENCLAMIDE; GLIMEPIRIDE PLUS METFORMIN; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; GLUCOSE; GLYCOSIDASE INHIBITOR; HEMOGLOBIN A1C; INSULIN; LEVOTHYROXINE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; METFORMIN; METFORMIN PLUS ROSIGLITAZONE; METFORMIN PLUS SAXAGLIPTIN; ORAL ANTIDIABETIC AGENT; PLACEBO; PLASMINOGEN ACTIVATOR INHIBITOR; PROTEINASE INHIBITOR; RNA DIRECTED DNA POLYMERASE INHIBITOR; ROSIGLITAZONE; SULFONYLUREA DERIVATIVE; THYROTROPIN; TRIACYLGLYCEROL; UNINDEXED DRUG; VON WILLEBRAND FACTOR;

ABDOMINAL PAIN; ALZHEIMER DISEASE; ANTIDIABETIC ACTIVITY; BODY WEIGHT; CANCER ADJUVANT THERAPY; CANCER PREVENTION; CANCER RECURRENCE; CARCINOGENESIS; CARDIOVASCULAR RISK; CHILDHOOD; CHILDHOOD OBESITY; DIABETES MELLITUS; DIARRHEA; DISEASE CONTROL; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG ELIMINATION; DRUG INDICATION; DRUG SAFETY; DRUG TOLERABILITY; EDEMA; ENDOTHELIAL DYSFUNCTION; FLATULENCE; GLYCEMIC CONTROL; HEADACHE; HEART FAILURE; HEART PROTECTION; HEMOSTASIS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HIV ASSOCIATED LIPODYSTROPHY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERTENSION; HYPOGLYCEMIA; IMPAIRED FASTING GLUCOSE; IMPAIRED GLUCOSE TOLERANCE; INCIDENCE; INFLAMMATION; INSULIN RESISTANCE; INSULIN SENSITIVITY; INTRAABDOMINAL FAT; ISCHEMIC HEART DISEASE; LACTIC ACIDOSIS; LIFESTYLE MODIFICATION; LIPID METABOLISM; METABOLIC DISORDER; MONOTHERAPY; MORTALITY; NAUSEA; NEOPLASM; NEUROPROTECTION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER DISEASE ACTIVITY SCORE; OBESITY; OXIDATIVE STRESS; PRACTICE GUIDELINE; PREGNANCY DIABETES MELLITUS; PREGNANT WOMAN; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; THYROID FUNCTION; TREATMENT CONTRAINDICATION; VOMITING; WEIGHT GAIN;

EID: 84873733300     PISSN: None     EISSN: 17585996     Source Type: Journal    
DOI: 10.1186/1758-5996-5-6     Document Type: Review

References (183)

1. Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents. Godarzi MO, Brier-Ash M, Diabetes Obes Metab 2005 5 654 665
2. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Shaw RJ, Lamia KA, Vasquez D, Science 2005 310 1642 1646 10.1126/science.1120781 16308421 (Pubitemid 41780780)
3. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. El-Mir MY, Nogueira V, Fontaine E, J Biol Chem 2000 275 223 228 10.1074/jbc.275.1.223 10617608 (Pubitemid 30038975)
4. Global prevalence of diabetes. Estimates for the year 2000 and projections for 2030. Wild S, Roglic G, Green A, Sicree R, King H, Diabetes Care 2004 27 1047 1053 10.2337/diacare.27.5.1047 15111519 (Pubitemid 38579764)
5. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. Guillies C, Abram KR, Lambert PC, Cooper NJ, Sutton AJ, BMJ 2007 334 299 10.1136/bmj.39063.689375.55 17237299 (Pubitemid 46293963)
6. Impaired glucose tolerance and impaired fasting glucose-a review of diagnosis, clinical implications and management. Petersen J, Mc Guire D, Diabetes Vasc Dis Res 2005 2 1 9 15 10.3132/dvdr.2005.007 (Pubitemid 40333199)
7. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. Diabetes Prevention Program Research Group, N Engl J Med 2002 346 393 403 11832527
8. Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program. Diabetes Prevention Program Research Group, Diabetes Care 2003 26 4 977 980 12663559
9. Indian diabetes prevention programme (IDPP). the Indian diabetes prevention programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Ramachandran A, Snehalatha C, Mukesh M, Diabetologia 2006 49 289 297 16391903 (Pubitemid 43185397)
10. The preventive effect of acarbose and metformin on the IGT population from becoming diabetes mellitus: a 3-year multicentral prospective study. Yang W, Lin L, Qi J, Chin J Endocrinol Metab 2001 17 131 134
11. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Diabetes Prevention Program Research Group, Lancet 2009 374 9702 1677 1686 10.1016/S0140-6736(09)61457-4 19878986
12. Low risk threshold for acquired diabetogenic factors in Asian Indians. Ramachandran A, Snehalatha C, Vijay V, Diab Res Clin Pract 2004 65 189 195 10.1016/j.diabres.2004.03.012 (Pubitemid 39141174)
13. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: The Da Qing IGT and Diabetes Study. Pan XR, Li GW, Hu YH, Diabetes Care 1997 20 537 544 10.2337/diacare.20.4.537 9096977
14. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Salpeter SR, Buckley NS, Kahn JA, Am J Med 2008 121 149 157 10.1016/j.amjmed.2007.09.016 18261504 (Pubitemid 351199461)
15. Treating prediabetes with metformin systematic review and meta-analysis. Lily M, Godwin M, Can Fam Physician 2009 55 363 369 19366942
16. Summary of revisions to the 2011 clinical practice recommendations. American Diabetes Association, Diabetes Care 2011 34 Suppl 1 3 21193626
17. Statement by an American association of clinical endocrinologists/ American college of endocrinology consensus panel on type 2 diabetes mellitus. An algorithm for glycemic control. Rodbard HW, Jellinger PS, Davidson JA, Endocr Pract 2009 15 6 540 559 19858063
18. Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Prospective Diabetes Study (UKPDS) Group, Lancet 1998 352 9131 854 865 9742977
19. Long-term effect of metformin on blood glucose control in non-obese patients with type 2 diabetes mellitus. Ito H, Ishida H, Takeuchi Y, Nutr Metab 2010 7 83 10.1186/1743-7075-7-83
20. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes: progressive requirement for multiple therapies (UKPDS 49). Turner RC, Cull CA, Frighi V, Holman RR, JAMA 1999 281 2005 2012 10.1001/jama.281.21.2005 10359389 (Pubitemid 29254858)
21. PRESERVE-beta: two-year efficacy and safety of initial combination therapy with nateglinide or glyburide plus metformin. Gerich J, Raskin P, Jean-Louis L, Diabetes Care 2005 28 2093 2099 10.2337/diacare.28.9.2093 16123472 (Pubitemid 41242450)
22. Effect of noninsulin Antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. Phung OJ, Scholle JM, Talwar M, Coleman CI, JAMA 2010 303 14 1410 1418 10.1001/jama.2010.405 20388897
23. Long-term efficacy and tolerability of add-on piogçitazone therapy to faliling monotherapy compared with addition of glicazide or metformin in patients with type 2 diabetes. Charbonnel B, Shernthaner G, Brunetti P, Diabetologia 2005 48 1093 1104 10.1007/s00125-005-1751-1 15889234 (Pubitemid 40909644)
24. One year glycemic control with sulphonylurea plus pioglitazone versus sulphonylurea plus metformin in patients with type 2 diabetes. Hanefeld M, Brunetti P, Schhernthaner GH, Diabetes Care 2004 27 141 147 10.2337/diacare.27. 1.141 14693980 (Pubitemid 38196723)
25. Efficacy of glimepiride/metformin combination versus glibenclamide/ metformin in patients with uncontrolled type 2 diabetes mellitus. González-Ortiza M, Guerrero-Romero J, Violante-Ortiz R, J Diabetes Complications 2009 23 376 379 10.1016/j.jdiacomp.2008.09.002 18849173
26. Decreased mortality associated with the use of metformin compared with sulfonylurea Monotherapy in type 2 diabetes. Johnson JA, Majumdar SR, Simpson SH, Diabetes Care 2002 25 2244 2248 10.2337/diacare.25.12.2244 12453968 (Pubitemid 41071035)
27. Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Evans JM, Ogston SA, Emslie-Smith A, Morris AD, Diabetologia 2006 49 930 936 10.1007/s00125-006-0176-9 16525843
28. Metformin for obese, insulin-treated diabetic patients: improvement in glycaemic control and reduction of metabolic risk factors. Giugliano D, Quatraro A, Consoli G, Eur J Clin Pharmacol 1993 44 107 112 10.1007/BF00315466 8453955 (Pubitemid 23047744)
29. Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial. Lund SS, Tarnow L, Frandsen M, BJ 2009 339 4324 10.1136/bmj.b4324
30. The use of metformin in type 1 diabetes: a systematic review of efficacy. Vella S, Buetow L, Royle P, Diabetologia 2010 53 5 809 820 10.1007/s00125-009- 1636-9 20057994
31. Metformin added to insulin therapy for type 1 diabetes mellitus in adolescents. Abdelghaffar S, Attia AM, Cochrane Database Syst Rev 2009 Issue 1 D006691
32. Rosiglitazone-metformin fixed-dose combination compared with uptritrated metformin alone in type diabetes mellitus:a 24 week, multicenter, randomized, double-blind, parallel-group study. Bailey CJ, Bagdonas A, Rubes J, Clin Ther 2005 27 1548 1561 10.1016/j.clinthera.2005.10.012 16330291 (Pubitemid 41739491)
33. Changes over time in glycemic control, insulin sensitivity, and beta-cell function in response to low-dose metformin and thiazolidinedione combination therapy in patients with impaired glucose tolerance. Retnakaran R, Qi Y, Harris SB, Hanley AJ, Zinman B, Diabetes Care 2011 34 7 1601 1604 10.2337/dc11-0046 21709296
34. ADOPT study: which first-line glucose-lowering oral medication in type 2 diabetes? Scheen AJ, Rev Med Liege 2007 62 1 48 52 17343130 (Pubitemid 351448375)
35. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M, Clin Pharmacol Ther 2009 85 513 519 10.1038/clpt.2008.250 19129749
36. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. List JF, Woo V, Morales E, Tang W, Fiedorek FT, Diabetes Care 2009 32 650 657 10.2337/dc08-1863 19114612
37. Reduction of the acute bioavailability of metformin by the α glycosidase inhibitor acarbose in normal man. Scheen AJ, de Magalhanes AC, Salvatore T, Eur J Clin Invest 1994 24 Suppl3 50 54 7818725 (Pubitemid 24260150)
38. Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes. Rosenstok J, Brown A, Fischer J, Diabetes Care 1998 21 2050 2055 10.2337/diacare.21.12.2050 9839093 (Pubitemid 28549150)
39. Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch CL, Cochrane Database Syst Rev 2008 2 D006739
40. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Mannucci E, Ognibene A, Cremasco F, Diabetes Care 2001 24 489 494 10.2337/diacare.24.3.489 11289473 (Pubitemid 32198418)
41. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. DeFronzo RA, Hissa MN, Garber AJ, for Saxagliptin Study Group, Diabetes Care 2009 32 9 1649 1655 10.2337/dc08-1984 19478198
42. Glycaemic efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors as add-on therapy to metformin in subjects with type 2 diabetes-a review and meta analysis. Deacon CF, Mannucci E, Ahrén B, Diabetes Obes Metab 2012 14 8 762 767 10.1111/j.1463-1326.2012. 01603.x 22471248
43. Population pharmacokinetics of metformin in late pregnancy. Charles B, Norris R, Xiao X, Hague W, Ther Drug Monit 2006 28 67 72 10.1097/01.ftd. 0000184161.52573.0e 16418696 (Pubitemid 44391696)
44. The safety of oral hypoglycemic agents in the first trimester of pregnancy. a meta-analysis. Gutzin SJ, Kozer E, Magee LA, Feig DS, Koren G, Can J Clin Pharmacol 2003 10 179 183 14712322 (Pubitemid 38181969)
45. Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis. Gilbert C, Valois M, Koren G, Fertil Steril 2006 86 658 663 10.1016/j.fertnstert.2006.02.098 16879826 (Pubitemid 44307028)
46. MiG trial investigators. Metformin versus insulin for the treatment of gestational diabetes. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP, N Engl J Med 2008 358 2003 2015 10.1056/NEJMoa0707193 18463376 (Pubitemid 351656455)
47. Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison. Moore LE, Briery CM, Clokey D, J Reprod Med 2007 52 1011 1015 18161398 (Pubitemid 350305083)
48. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition at 2 years of age. Rowan JA, Rush EC, Obolonkin V, Battin M, Wouldes T, Hague WM, Diabetes Care 2011 34 2279 2284 10.2337/dc11-0660 21949222
49. Type 2 diabetes and impaired glucose tolerance in European children and adolescents with obesity- a problem that is no longer restrited to minority groups. Wiegand S, Maikowski U, Blankenstein O, Bierbermann H, Tarnow P, Grutes A, Eur J Endocrinol 2004 151 199 206 10.1530/eje.0.1510199 15296475 (Pubitemid 39207015)
50. Clinical presentation and treatment of type 2 diabetes in children. Pinhas-Hamiel O, Zeitler P, Pediatr Diabetes 2007 8 Suppl. 9 16 27 17991129 (Pubitemid 350066644)
51. Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial. Jones KL, Arslanian S, Peterokova VA, Park JS, Tomlinson MJ, Diabetes Care 2002 25 89 94 10.2337/diacare.25.1.89 11772907 (Pubitemid 41070789)
52. Glimepiride Versus Metformin as Monotherapy in Pediatric Patients With Type 2 Diabetes.A randomized, single-blind comparative study. Gottschalk M, Danne T, Vlajnic A, Cara J, DiabetesCare 2007 30 790 794 (Pubitemid 46556568)
53. Early signs of cardiovascular disease in youth with obesityand type 2 diabetes. Gungor N, Thompson T, Sutton-Tyrrell K, Janosky J, Arslanian S, Diabetes Care 2005 28 5 1219 1221 10.2337/diacare.28.5.1219 15855596 (Pubitemid 40616642)
54. Relationship of childhood obesity to coronary heart disease risk factors in adulthood: the Bogalusa Heart Study. Freedman DS, Khan LK, Dietz WH, Srinivasan SR, Berenson GS, Pediatrics 2001 108 3 712 718 10.1542/peds.108.3.712 11533341 (Pubitemid 32786603)
55. Nonalcoholic steatohepatitis in children. Rashid M, Roberts EA, J Pediatr Gastroenterol Nutr 2000 30 48 53 10.1097/00005176-200001000-00017 10630439 (Pubitemid 30349945)
56. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Targher G, Bertolini L, Poli F, Diabetes 2005 54 3541 3546 10.2337/diabetes.54.12.3541 16306373 (Pubitemid 43334347)
57. Cardiorespiratory fitness in young adulthood and the development of cardiovascular disease risk factors. Carnethon MR, Gidding SS, Nehgme R, Sidney S, JAMA 2003 290 3092 3100 10.1001/jama.290.23.3092 14679272 (Pubitemid 37548115)
58. Prevalence of fatty liver in children and adolescents. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C, Pediatrics 2006 118 1388 1393 10.1542/peds.2006-1212 17015527 (Pubitemid 46393782)
59. Insulin sensitivity among obese children and adolescents, according to degree of weight loss. Reinehr T, Kiess W, Kappellen T, Andler W, Pediatrics 2004 114 1569 1573 10.1542/peds.2003-0649-F 15574616 (Pubitemid 41754919)
60. Long-TermEffects of metformin and lifestyle modification on nonalcoholic fatty liver disease obese adolescents. Tock L, Damaso A, de Piano A, Carnier J, J Obes 2010 831901 6 Article ID 831901
61. Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance. Burgert TS, Duran EJ, Goldberg-Gell R, Dziura J, Yeckel CW, Katz S, Tamborlane WV, Caprio S, Pediatr Diabetes 2008 9 567 576 10.1111/j.1399-5448.2008.00434.x 18761646
62. Metformin for obesity in children and adolescents: a systematic review. Park M, Kinra S, Ward K, White B, Viner R, Diabetes Care 2009 32 1743 1745 10.2337/dc09-0258 19502540
63. Heart rate recovery after submaximal exercise testing asa predictor of mortality in a cardiovascularly healthy cohort. Cole CR, Foody JM, Blackstone EH, Lauer MS, Ann Intern Med 2000 132 552 555 10744592 (Pubitemid 30171895)
64. Heart rate recovery after exercise is related to the insulin resistance syndrome and heart rate variability in elderly men. Lind L, Andren B, Am Heart J 2002 144 666 672 12360163
65. Treatment of nonalcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. Nadeau KJ, Ehlers LB, Zeitler PS, Love-Osborne K, Pediatr Diabetes 2009 10 5 13 10.1111/j.1399-5448. 2008.00450.x 18721166
66. Interventions for treating obesity in children. Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O'Malley C, Stolk RP, Summerbell CD, Cochrane Database Syst Rev 2009 1 D001872
67. Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham Study. Kannel WB, McGee DL, Diabetes Care 1979 2 120 126 10.2337/diacare.2.2.120 520114 (Pubitemid 9238733)
68. Wingard DL, Barrett-Connor E, Heart disease and diabetes Washington, D.C: GPO 2 NationalDiabetes Data Group. Diabetes in America. 1995 429 48 NIH publication no.95-1468
69. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M, N Engl J Med 1998 339 229 234 10.1056/NEJM199807233390404 9673301 (Pubitemid 28350165)
70. National Cholesterol Education Program (NCEP) Expert Panel onDetection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).Third Report of the NationalCholesterol Education Program (NCEP) Expert Panel on Detection. Krempf M, Parhofer KG, Steg G, Circulation 2002 106 3143 3421 12485966
71. Is diabetes a coronary risk equivalent? Systematic review and meta-analysis. Bulugahapitiya U, Siyambalapitiya S, Sithole J, Idris I, Diabet Med 2009 26 142 148 10.1111/j.1464-5491.2008.02640.x 19236616
72. Use of metformin in ischemic cardiopathy. Sgambato S, Varricchio M, Tesauro P, Passariello N, Carbone L, Clin Ther 1980 94 77 85
73. 10-year follow up of intensive glucose control in type 2 diabetes. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA, N Engl J Med 2008 359 1577 1589 10.1056/NEJMoa0806470 18784090
74. Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention. Kao J, Tobis J, Mc Clelland RL, Am J Cardiol 2004 93 1347 1350 10.1016/j.amjcard.2004.02.028 15165912 (Pubitemid 38692459)
75. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Kooy A, de Jager J, Lehert P, Arch Intern Med 2009 169 616 625 10.1001/archinternmed.2009. 20 19307526
76. Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries. Jadhav S, Ferrell W, Greer IA, Petrie JR, Cobbe SM, Sattar N, J Am Coll Cardiol 2006 48 956 963 10.1016/j.jacc.2006.04.088 16949486 (Pubitemid 44292455)
77. Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. Boussageon R, Supper I, Bejan-Angoulvant T, PLoS Med 2012 9 4 1001204 10.1371/journal.pmed.1001204 22509138
78. Diabetes, left ventricular systolic dysfunction, and chronic heart failure. MacDonald MR, Petrie MC, Hawkins NM, Eur Heart J 2008 10 1224 1240 10.1016/j.ejheart.2008.09.017 (Pubitemid 351768135)
79. Metformin-associated lactic acidosis. Hulisz DT, Bonfiglio MF, Murray RD, J Am Board Fam Pract 1998 11 233 236 9625516 (Pubitemid 29187385)
80. Food and Drug Administration. Product label approval: metformin 2006 http://packageinserts.bms.com/pi/piglucophage.pdf
81. Thiazolinediones, metformin, and outcomes in older patients with diabetes and heart failure. Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM, Circulation 2005 111 583 590 10.1161/01.CIR.0000154542.13412.B1 15699279 (Pubitemid 40216485)
82. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA, Diabetes Care 2005 28 2345 2351 10.2337/diacare.28.10.2345 16186261 (Pubitemid 41384275)
83. Metformin and heart failure: never say never again. Papanas N, Maltezos E, Mikhailidis DP, Expert Opin Pharmacother 2012 1 1 8
84. Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. Rachmani R, Slavachevski I, Levi Z, Zadok B, Kedar Y, Ravid M, Eur J Intern Med 2002 13 428 433 10.1016/S0953-6205(02)00131-0 12384131
85. Metformin Therapy and Outcomes in Patients With Advanced Systolic Heart Failure and Diabetes. Shah DD, Fonarow GC, Horwich TB, J Card Fail 2010 16 3 200 206 10.1016/j.cardfail.2009.10.022 20206893
86. Metformin inhibits Proinflammatory Responses and Nuclear Factor κß in Human Vascular Wall Cells. Isoda K, Young J, Zirlik A, Arterioscler Thromb Vasc Biol 2006 26 611 617 16385087
87. Lifestyle Intervention or Metformin on Inflammation and Coagulation in Participants With Impaired Glucose Tolerance. The Diabetes Prevention Program Research Group Intensive, Diabetes 2005 54 5 1566 1572 15855347
88. Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. De Jager J, Kooy A, Lehert P, J Intern Med 2004 256 1 14 10.1111/j.1365-2796.2004.01328.x 15189360 (Pubitemid 38813614)
89. Improved endothelial function with metformin in type 2 diabetes mellitus. Mather KJ, Verma S, Anderson TJ, J Am Coll Cardiol 2001 37 5 1344 1350 10.1016/S0735-1097(01)01129-9 11300445 (Pubitemid 32295597)
90. Metformin improves endothelial function in patients with metabolic syndrome. Vitale C, Mercuro G, Cornoldi A, Fini M, J Intern Med 2005 258 250 256 10.1111/j.1365-2796.2005.01531.x 16115299 (Pubitemid 41243057)
91. Beneficial effects of metformin on haemostasis and vascular function in man. Grant PJ, Diabetes Metab 2003 29 6S 44 52 12629447
92. The effect of dimethylbiguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation. Standeven KF, Ariens RA, Whitaker P, Diabetes 2002 51 189 197 11756340 (Pubitemid 34517997)
93. Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: the BIGPRO1 Study. Biguanides and the Prevention of the Risk of Obesity. Charles MA, Morange P, Eschwege E, Diabetes Care 1998 21 1967 1972 10.2337/diacare.21.11.1967 9802752 (Pubitemid 28478302)
94. Lifestyle Intervention and Metformin for Treatment of Antipsychotic-Induced Weight Gain A Randomized Controlled Trial. Wu RR, Zhao JP, Jin H, JAMA 2008 299 2 185 193 10.1001/jama.2007.56-b 18182600
95. Metformin reduces weight, centripetalobesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Glueck CJ, Fontaine RN, Wang P, Metabolism 2001 50 856 861 10.1053/meta.2001.24192 11436194 (Pubitemid 32700469)
96. Metformin, but not pioglitazone, decreases postchallenge plasma ghrelin levels in type 2 diabetic patients: a possible role in weight stability? Kusaka I, Nagasaka S, Horie H, Ishibashi S, Diabetes Obes Metab 2008 10 1039 1046 10.1111/j.1463-1326.2008.00857.x 18355332
97. Metformin in the Treatment of HIV Lipodystrophy Syndrome A Randomized Controlled Trial. Hadigan C, Corcoran C, Basgoz N, JAMA 2000 284 472 477 10.1001/jama.284.4.472 10904511 (Pubitemid 30484481)
98. The efficacy and safety of insulin-sensitizing drugs in HIV-associated lipodystrophy syndrome: a meta-analysis of randomized trials. Sheth S, Larson L, BMC Infect Dis 2010 10 183 10.1186/1471-2334-10-183 20573187
99. Metformin. Bailey CJ, Turner RC, N Engl J Med 1996 334 574 579 10.1056/NEJM199602293340906 8569826 (Pubitemid 26066132)
100. An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats. Faure P, Rossini E, Wiernsperger N, Diabetes 1999 48 353 357 10.2337/diabetes.48.2.353 10334313 (Pubitemid 29061110)
101. Metformin inhibition of glycation processes. Beisswenger P, Rugiero-Lopez D, Diabetes Metab 2003 29 6S 95 103
102. Metformin induces oxidative stress in white adipocytes and raises uncoupling proten levels. Anedda A, Rial E, Gonzalez Barroso, J Endocrinol 2008 199 33 40 10.1677/JOE-08-0278 18687824
103. Sirtuin 1-mediated cellular metabolic memory of high glucose via the LKB1/AMPK/ROS pathway and therapeutic effects of metformin. Zheng Z, Chen H, Li J, Li T, Zheng B, Zheng Y, Jin H, He Y, Gu Q, Xun X, Diabetes 2012 61 1 217 228 10.2337/db11-0416 22124463
104. Glycemic durability of rosiglitazone, metformin or glyburide monotherapy. Kahn SE, Haffner SM, Heise MA, N Engl J Med 2006 355 2427 2443 10.1056/NEJMoa066224 17145742 (Pubitemid 44903747)
105. Role of metformin for weight management in patients without type 2 diabetes. Desilets AR, Dhakal-Karki S, Dunican KC, Ann Pharmacother 2008 42 817 826 10.1345/aph.1K656 18477733 (Pubitemid 351778088)
106. The effects of medications used for the management of diabetes and obesity on postprandial lipid metabolism. Eleftheriadou I, Grigoropoulou P, Katsilambros N, Tentolouris N, Curr Diabetes Rev 2008 4 340 356 10.2174/157339908786241133 18991602
107. Does metformin decrease blood pressure in patients with type 2 diabetes intensively treated with insulin? Wulffelé MG, Kooy A, Lehert P, Bets D, Donker A, Stehouwer C, Diabet Med 2005 22 907 10.1111/j.1464-5491.2005.01554.x 15975107 (Pubitemid 40949534)
108. Effects of insulin on vascular tone and sympathetic nervous system in NIDDM. Tack CJ, Smits P, Willemsen JJ, Lenders JW, Thien T, Lutterman JA, Diabetes 1996 45 15 22 10.2337/diabetes.45.1.15 8522054 (Pubitemid 26010417)
109. Molecular mechanisms of insulin resistance in arterial hypertension. Sechi LA, Bartoli E, Blood Press Suppl 1996 1 47 54 9162438 (Pubitemid 26146882)
110. Cardiovascular risk factors associated with insulin resistance: effects of oral antidiabetic agents. Granberry MC, Fonseca VA, Am J Cardiovasc Drugs 2005 5 201 209 10.2165/00129784-200505030-00006 15901207 (Pubitemid 40994272)
111. Effects of 1-year treatment with metformin on metabolic and cardiovascular risk factors in non-diabetic upper-body obese subjects with mild glucose anomalies: a post-hoc analysis of the BIGPRO1 trial. Fontbonne A, Diouf I, Baccara-Dinet M, Eschwege E, Charles A, Diabetes Metab 2009 35 385 391 10.1016/j.diabet.2009.03.005 19665415
112. Thyrotropin Suppression by Metformin. Vigersky R, Filmore-Nassar A, Allan R, J Clin Endocrinol Metab 2006 91 225 227 10.1210/jc.2005-1210 16219720 (Pubitemid 43069142)
113. TSH-lowering effect of metformin in type 2 diabetic patients differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients. Capelli C, Rotondi M, Pirola I, Agosti B, Gandossi E, Diabetes Care 2009 32 1589 1590 10.2337/dc09-0273 19502536
114. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with HIV disease. Triant VA, Lee H, Hadigan C, Grinspoon SK, J Clin Endocrinol Metab 2007 92 2506 2512 10.1210/jc.2006-2190 17456578 (Pubitemid 47037350)
115. Adiponectin and HIV-lipodystrophy:taking HAART. Kinlaw WB, Marsh B, Endocrinology 2004 145 484 486 14739152
116. A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy. Moyle GJ, Sabin CA, Cartledge J, Acquir Immune Defic Syndr 2006 20 2043 2050 (Pubitemid 44611057)
117. Impaired glucose tolerance, b cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. Behrens G, Dejam A, Schmidt H, Acquir Immune Defic Syndr 1999 13 63 F70
118. A randomized placebo-controlled trial of metformin for the treatment of HIV lipodystrophy. Kohli R, Shevitz A, Gorbach S, Wanke C, HIV Med 2007 8 420 426 10.1111/j.1468-1293.2007.00488.x 17760733 (Pubitemid 47335264)
119. Comparison of Rosiglitazone and Metformin for treating HIV Lipodistrophy. van Wijk, de Koning E, Castro M, Ann Inter Med 2005 143 337 346
120. AMP-Activated Protein Kinase (AMPK) Molecular Crossroad for Metabolic Control and Survival of Neurons. Spasic MR, Callaerts P, Norga KK, Neuroscientist 2009 15 4 309 316 10.1177/1073858408327805 19359670
121. AMPactivated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation. Culmsee C, Monnig J, Kemp BE, Mattson MP, J Mol Neurosci 2001 17 45 58 10.1385/JMN:17:1:45 11665862 (Pubitemid 32928285)
122. Metformina e AMPK: Um Antigo Fármaco e Uma Nova Enzima no Contexto da Síndrome Metabólica. Santomauro Júnior AC, Ugolini MR, Santomauro AT, Souto RP, Arq Bras Endocrinol Metabol 2008 52 1 120 125 10.1590/S0004-27302008000100017 18345405
123. Neuroprotective Role of Antidiabetic Drug Metformin Against Apoptotic Cell Death in Primary Cortical Neurons. El-Mir MY, Detaille D, Villanueva G, J Mol Neurosci 2008 34 1 77 87 10.1007/s12031-007-9002-1 18040888 (Pubitemid 351378091)
124. Oxidative stress in neurodegeneration: Cause or consequence? Andersen JK, Nat Med 2004 10 18 S25 10.1038/nrn1434 15298006
125. Mitochondrial control of cell death. Kroemer G, Reed JC, Nat Med 2000 6 513 519 10.1038/74994 10802706 (Pubitemid 30305900)
126. Metformin prevents high glucose-induced endothelial cell death through a mitochondrial permeability transition-dependent process. Detaille D, Guigas B, Chauvin C, Diabetes 2005 54 2179 2187 10.2337/diabetes.54.7.2179 15983220 (Pubitemid 40911282)
127. The role of insulin receptor signaling in the brain. Plum L, Schubert M, Bruning JC, Trends Endocrinol Metab 2005 16 59 65 10.1016/j.tem.2005.01.008 15734146 (Pubitemid 40270851)
128. Insulin signaling in the central nervous system: learning to survive. van der Heide LP, Ramakers GM, Smidt MP, Prog Neurobiol 2006 79 205 221 10.1016/j.pneurobio.2006.06.003 16916571 (Pubitemid 44331498)
129. Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer's-like change. Gupta A, Bisht B, Dey CS, Neuropharmacology 2011 60 910 920 10.1016/j.neuropharm.2011.01.033 21277873
130. The cell biology of ßamyloid precursor protein and presenilin in Alzheimer's disease. Selkoe DJ, Trends Cell Biol 1998 8 447 453 10.1016/S0962-8924(98)01363-4 9854312 (Pubitemid 28529718)
131. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Chen Y, Zhoua K, Wanga R, Liua Y, PNAS 2009 106 10 3907 3912 10.1073/pnas.0807991106 19237574
132. Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Wang J, Gallagher D, De Vito L, Cell Stem Cell 2012 11 23 35 10.1016/j.stem.2012.03.016 22770240
133. Metformin and cancer: licence to heal? Papanas N, Maltezos E, Mikhailidis DP, Expert Opin Investig Drugs 2010 19 913 917 10.1517/13543784.2010.499122 20557275
134. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. Larsson SC, Orsini N, Wolk A, J Natl Canc Ins 2005 97 1679 1687 10.1093/jnci/dji375 (Pubitemid 41672234)
135. Anti-diabetic therapies affect risk of pancreatic cancer. Li D, Yeung SJ, Hassan MM, Konopleva M, Abbruzzese JL, Gastroenterology 2009 137 2 482 488 10.1053/j.gastro.2009.04.013 19375425
136. Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma. Donadon V, Balbi M, Valent F, Avogaro A, World J Gastroenterol 2010 16 24 3025 3032 10.3748/wjg.v16.i24.3025 20572306
137. New users of metformin area at low risk of incident cancer: a cohort study among people with type 2 diabetes. Libby G, Donnelly LA, Donnan PT, Diabetes Care 2009 32 1620 1625 10.2337/dc08-2175 19564453
138. Metformin associated with lower cancer mortality in type 2 diabetes ZODIAC-16. Landman GW, Kleefstra N, van Hateren KJ, Diabetes Care 2010 33 322 326 10.2337/dc09-1380 19918015
139. The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. Lee JH, Kim TI, Jeon SM, Int J Cancer 2011 12 1 24
140. Diabetes mellitus and the risk of cancer. Results from a large-scale population-based cohort study. Inoue M, Iwasaki M, Otami T, Arch Intern Med 2006 166 1871 1877 10.1001/archinte.166.17.1871 17000944 (Pubitemid 44455170)
141. Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. Grimberg A, Cohen P, J Cell Physiol 2000 183 1 9 10.1002/(SICI)1097-4652(200004)183:1<1::AID-JCP1>3.0.CO;2-J 10699960 (Pubitemid 30130219)
142. Cancer and diabetes: are we ready for prime time? Smith U, Gale EAU, Diabetologia 2010 53 1541 1544 10.1007/s00125-010-1815-8 20549181
143. Status of PI3K inhibition and biomarker development in cancer therapeutics. Markman B, Atzori F, Perez-Garcia J, Tabernero J, Baselga J, Ann Oncol 2010 21 683 691 10.1093/annonc/mdp347 19713247
144. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPasedependent manner. Kalender A, Selvaraj A, Kim SY, Cell Metab 2010 11 390 401 10.1016/j.cmet.2010.03.014 20444419
145. Metformin and reduced risk of cancer in diabetic patients. Evans J, Donelly L, Emslie A, BMJ 2005 330 7503 1304 1305 10.1136/bmj.38415.708634.F7 15849206 (Pubitemid 40813563)
146. Long-term metformin Use is associated with decreased risk of breast cancer. Bodmer M, Meier C, Krähenbühl S, Diabetes Care 2010 33 1304 1308 10.2337/dc09-1791 20299480
147. Increased cancer-related mortality for patients with type 2 diabetes who usesulfonylureas or insulin. Bowker SL, Majumdar SR, Veugelers P, Johnson JA, Diabetes Care 2006 29 254 258 10.2337/diacare.29.02.06.dc05-1558 16443869 (Pubitemid 44106500)
148. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Ben Sahra I, Laurent K, Loubat A, Oncogene 2008 27 3576 3586 10.1038/sj.onc.1211024 18212742 (Pubitemid 351793803)
149. Insulin and insulin-like growth factor signaling in neoplasia. Pollak M, Nat Rev Cancer 2008 8 915 928 10.1038/nrc2536 19029956
150. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M, Cancer Res 2006 66 10269 10273 10.1158/0008-5472.CAN-06-1500 17062558 (Pubitemid 44799743)
151. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA, Cell Cycle 2009 8 88 96 10.4161/cc.8.1.7499 19106626
152. Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. Lund SS, Tarnow L, Stehouwer CD, Eur J Endocrinol 2008 158 631 641 10.1530/EJE-07-0815 18426821 (Pubitemid 351639600)
153. AMPK and p53 help cells through lean times. Thoreen CC, Sabatini DM, Cell Metab 2005 1 287 288 10.1016/j.cmet.2005.04.009 16054073 (Pubitemid 43960621)
154. Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1. Zhuang Y, Miskimins W, J Mol Signal 2008 3 18 10.1186/1750-2187-3-18 19046439
155. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Pearce EL, Walsh MC, Cejas PJ, Nature 2009 460 103 107 10.1038/nature08097 19494812
156. Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer. Jiralerspong S, Palla S, Giordano S, J Clin Oncol 2009 27 3297 3302 10.1200/JCO.2009.19.6410 19487376
157. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Hirsh H, Iliopoulos D, Tsichlis P, Stuh K, Cancer Res 2009 69 19 7507 7511 10.1158/0008-5472.CAN-09- 2994 19752085
158. Metformin therapy and clinical uses. Scarpello J, Howlett H, Diabetes Vasc Dis Res 2008 5 157 167 10.3132/dvdr.2008.027
159. Fatal phenformin-associated lactic acidosis. Rosand J, Friedberg J, Yang J, Ann Intern Med 1997 127 170 9230024
160. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE, Cochrane Database Syst Rev 2010 1 D002967 20091535
161. Metformin, heart failure and lactic acidosis: is Metformin absolutely contraindicated? Tahrani AA, Varghese GI, Scarpello JH, Hanna FWF, BMJ 2007 355 508 512 (Pubitemid 47401613)
162. Use of metformin in the setting of mild-to-moderate renal insufficiency. Lipska KJ, Bailey CJ, Inzucchi SE, Diabetes Care 2011 34 6 1431 1437 10.2337/dc10-2361 21617112
163. Novel assay of metformin levels in patients with type 2 diabetes mellitus and varying levels of renal function. Frid A, Sterner GN, Londahl M, Diabetes Care 2010 33 1291 1293 10.2337/dc09-1284 20215446
164. Metformin: a review of its pharmacological properties and therapeutic use. Metformin LS, Diabetes Metab 1979 5 233 245
165. Metformin: a review of its metabolic effects. Cusi K, DeFronzo RA, Diabetes Rev 1998 6 89 131 (Pubitemid 28554676)
166. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Bauman WA, Shaw S, Jayatilleke E, Diabetes Care 2000 23 1227 1231 10.2337/diacare.23.9.1227 10977010
167. Megaloblastic anemia due to vitamin B12 malaborsption associated with long-term metformin treatment. Callaghan TS, Hadden DR, Tomkin GH, Br Med J 1980 280 1214 1215 10.1136/bmj.280.6225.1214 7388472 (Pubitemid 10117808)
168. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomized placebo controlled trial. Jager J, Kooy A, Lehert P, Wulffelé M, BMJ 2010 340 2181 10.1136/bmj.c2181 20488910
169. Risk Factors of Vitamin B12 Deficiency in Patients Receiving Metformin. Wei Ting RZ, Szeto CC, Chan M, Ma K, Arch Intern Med 2006 166 1975 1979 10.1001/archinte.166.18.1975 17030830 (Pubitemid 44537177)
170. Leucocytoclastic vasculitis and pneumonitis induced by metformin. Klapholz L, Leitersdorf E, Weinrauch L, BMJ 1986 293 483 3091171 (Pubitemid 16051224)
171. Cholestatic jaundice associated with the use of metformin. Desilets DJ, Shorr AF, Moran KA, Holtzmuller KC, Am J Gastroenterol 2001 96 2257 2258 10.1111/j.1572-0241.2001.03972.x 11467664 (Pubitemid 32660929)
172. Haemolytic anaemia due to metformin. Kashyap AS, Kashyap S, Postgrad Med J 2000 76 125 126 10.1136/pmj.76.892.125 10644400 (Pubitemid 30069459)
173. Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women. Giugliano D, De Rosa N, Di Maro G, Diabetes Care 1993 16 1387 1390 10.2337/diacare.16.10.1387 8269798
174. Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years (UKPDS 13). United Kingdom Prospective Diabetes Study (UKPDS) Group, BMJ 1995 310 83 88 7833731
175. Glucophage® and Glucophage XRproduct information. Bristol-Myers Squibb Company 2003 Available at: http://www.drugs.com/pro/glucophage.html 23513016
176. Oral antidiabetic combination therapy with sulphonylureas and metformin. Haupt E, Knick B, Koschinsky T, Liebermeister H, Schneider J, Hirche H, Diabete Metab 1991 17 224 231 1936481
177. Management of hyperglycaemiain 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. Nathan DM, Buse JB, Davidson MB, Diabetologia 2006 49 1711 1721 10.1007/s00125-006-0316-2 16802130 (Pubitemid 44025023)
178. The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type 2 diabetes. Grant P, Diabetes Care 1996 19 64 66 10.2337/diacare.19.1.64 8720537
179. Efficacy of metformin in type 2 diabetes: results of a double-blind, placebo-controlled, dose-response trial. Garber AJ, Duncan TG, Goodman AM, Millus DJ, Rohlf JL, Am J Med 1997 103 491 497 10.1016/S0002-9343(97)00254-4 9428832 (Pubitemid 28018651)
180. The phamacokinetics and pharmacodynamics of extended-release metformin tablets vs immediate-release metformin in subjects with type 2 diabetes. Donahue S, Marathe P, Guld T, Meeker J, Diabetes 2002 51 Suppl 2 468
181. Assessment of efficacy and tolerability of oncedaily extended release metformin in patients with type 2 diabetes mellitus. Levy J, Cobas RA, Gomes MB, Diabetol Metab Syndr 2010 2 16 10.1186/1758-5996-2-16 20298568
182. Safety and efficacy of novel extended-release formulation of metformin in patients with type 2 diabetes. Raz I, Delaet I, Goyvaerts H, Diabetes 2000 49 Suppl 1 363
183. Adherence in patients transferred from immediate release metformin to a sustained release formulation: a population-based study. Donnelly LA, Morris AD, Pearson ER, Diabetes Obes Metab 2009 11 338 342 10.1111/j.1463-1326.2008.00973. x 19267712