Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: Randomised placebo controlled trial

BMJ (Online)

Volumn 340, Issue 7757, 2010, Pages 1177-

  De Jager, Jolien ^a,b   Kooy, Adriaan ^b   Lehert, Philippe ^c   Wulffelé, Michiel G ^b   Van Der Kolk, Jan ^b   Bets, Daniël ^d   Verburg, Joop ^b   Donker, Ab J M ^e   Stehouwer, Coen D A ^f  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

^b Bethesda General Hospital   (Netherlands)

^c Facultes Universitaires Catholiques de Mons   (Belgium)

^d Clinical Research and Development   (Netherlands)

^e VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^f MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

CYANOCOBALAMIN; FOLIC ACID; HOMOCYSTEINE; INSULIN; METFORMIN; PLACEBO;

ADULT; AGED; ARTICLE; BLOOD LEVEL; BODY MASS; CIGARETTE SMOKING; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CYANOCOBALAMIN DEFICIENCY; DRUG WITHDRAWAL; FEMALE; FOLIC ACID BLOOD LEVEL; HUMAN; INCIDENCE; LONG TERM CARE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NETHERLANDS; NON INSULIN DEPENDENT DIABETES MELLITUS; OUTPATIENT DEPARTMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; UNSPECIFIED SIDE EFFECT; VITAMIN BLOOD LEVEL;

AGED; DIABETES MELLITUS, TYPE 2; FEMALE; FOLIC ACID; HOMOCYSTEINE; HUMANS; HYPOGLYCEMIC AGENTS; LONG-TERM CARE; MALE; METFORMIN; MIDDLE AGED; RISK FACTORS; VITAMIN B 12; VITAMIN B 12 DEFICIENCY;

EID: 77953929752     PISSN: None     EISSN: 17561833     Source Type: Journal    
DOI: 10.1136/bmj.c2181     Document Type: Article

References (27)

1. Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med 2002;137:25-33.
2. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854-65.
3. Kooy A, de Jager J, Lehert P, Bets D, Wulffele MG, Donker AJM, et al. Long-term effects of metformin on metabolism and microvascular andmacrovascular disease in patients with type 2 diabetesmellitus. Arch Intern Med 2009;169:616-25.
4. Pyorala K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev 1987;3:463-524.
5. DeFronzo RA, Goodman AM, the Multicenter Metformin Study Group. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 1995;333:541-9.
6. Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227-31.
7. Ting RZ-W, Szeto CC, Chan MH-M, Ma KK, Chow KM. Risk factors of vitamin B12 deficiency in patients receiving metformin. Arch Intern Med 2006;166:1975-9.
8. Carlsen SM, Folling I, Grill V, Bjerve KS, Schneede J, Refsum H. Metformin increases total serum homocysteine levels in nondiabetic male patients with coronary heart disease. Scand J Clin Lab Invest 1997;57:521-7.
9. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995;274:1049-57.
10. Nygård O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997;337:230-6.
11. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 1998;338:1042-50.
12. Wulffelé MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate, and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med 2003;254:455-63.
13. Pongchaidecha M, Srikusalanukul V, Chattananon A, Tanjariyaporn S. Effect of metformin on plasma homocysteine, vitamin B12 and folic acid: a cross-sectional study in patients with type 2 diabetes mellitus. J Med Assoc Thai 2004;87:780-7.
14. Sahin M, Tutuncu NB, Ertugrul D, Tanaci N, Guvener ND. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications 2007;21:118-23. (Pubitemid 46304266)
15. Hermann LS, Kalén J, Katzman P, Lager I, Nilsson A, Norrhamn O, et al. Long-term glycaemic improvement after addition of metformin to insulin in insulin-treated obese type 2 diabetes patients. Diabetes Obes Metab 2001;3:428-34. (Pubitemid 34030862)
16. Wulffelé MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, et al. Combination of insulin and metformin in the treatment of type 2 diabetes. Diabetes Care 2002;25:2133-40.
17. Marks PW, Zuckerberg LR. Case 30-2004: a 37-year-old woman with paresthesias of the arms and legs. NEngl J Med2004;351:1333-41.
18. Adams JF, Clark JS, Ireland JT, Kesson CM, Watson WS. Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. Diabetologia 1983;24:16-8.
19. Tomkin GH, Hadden DR, Weaver JA, Montgomery DA. Vitamin-B12 status of patients on long-term metformin therapy. BMJ 1971;2:685-7.
20. British Committee for Standards in Haematology guidelines. http://www.bcshguidelines.com/.
21. Healton EB, Savage DG, Brust JC, Garrett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine 1991;70:229-45.
22. Stabler SP, Allen RH, Savage DG, Lindenbaum J. Clinical spectrum and diagnosis of cobalamin deficiency. Blood 1990;76:871-81.
23. Kuzminski AM, Giacco AJD, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood 1998;92:1191-8.
24. Hermann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int 2008;105:680-5.
25. Derosa G, Mugellini A, Ciccarelli L, Crescenzi G, Fogari R. Comparison of glycaemic control and cardiovascular risk profile in patients with type 2 diabetes during treatment with either repaglinide or metformin. Diabetes Res Clin Pract 2003;60:161-9. (Pubitemid 36561617)
26. Hoogeveen EK, Kostense PJ, Jakobs C, Bouter LM, Heine RJ, Stehouwer CDA. Does metformin increase the serum total homocysteine level in non-insulin-dependent diabetes mellitus? J Intern Med 1997;242:389-94.
27. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency. Arch Intern Med 1999;159:1289-98.