OBJECTIVE:Metformin is a key treatment option in type 2 diabetes. However, metformin may decrease vitamin B12 levels and increase levels of homocysteine, a cardiovascular risk factor. We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homocysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin. DESIGN:Placebo-controlled, randomized trial. MEASUREMENTS: at baseline and 16 weeks later. SETTING: This trial was conducted in the outpatient clinics of three general hospitals in The Netherlands. SUBJECTS: A total of 745 patients with type 2 diabetes, treated with insulin and not known with a contraindication for the use of metformin, were approached; 390 gave informed consent and entered the study. Thirty-seven subjects dropped out (12 placebo and 25 metformin users). INTERVENTION: Addition of metformin or placebo to insulin therapy. PRIMARY OUTCOME PARAMETERS: Serum homocysteine, folate, vitamin B12, indices of glycaemic control and body weight. RESULTS: Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P=0.039) and with decreases in folate [-7% (-1.4 to -13); P=0.024] and vitamin B12 [-14% (-4.2 to -24); P<0.0001]. In addition, the increase in homocysteine could be explained by the decreases in folate and vitamin B12. CONCLUSION: In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine. The clinical significance of these findings remains to be investigated.
RCT Entities:
OBJECTIVE:Metformin is a key treatment option in type 2 diabetes. However, metformin may decrease vitamin B12 levels and increase levels of homocysteine, a cardiovascular risk factor. We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homocysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin. DESIGN: Placebo-controlled, randomized trial. MEASUREMENTS: at baseline and 16 weeks later. SETTING: This trial was conducted in the outpatient clinics of three general hospitals in The Netherlands. SUBJECTS: A total of 745 patients with type 2 diabetes, treated with insulin and not known with a contraindication for the use of metformin, were approached; 390 gave informed consent and entered the study. Thirty-seven subjects dropped out (12 placebo and 25 metformin users). INTERVENTION: Addition of metformin or placebo to insulin therapy. PRIMARY OUTCOME PARAMETERS: Serum homocysteine, folate, vitamin B12, indices of glycaemic control and body weight. RESULTS: Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P=0.039) and with decreases in folate [-7% (-1.4 to -13); P=0.024] and vitamin B12 [-14% (-4.2 to -24); P<0.0001]. In addition, the increase in homocysteine could be explained by the decreases in folate and vitamin B12. CONCLUSION: In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine. The clinical significance of these findings remains to be investigated.
Authors: Vanita R Aroda; Sharon L Edelstein; Ronald B Goldberg; William C Knowler; Santica M Marcovina; Trevor J Orchard; George A Bray; David S Schade; Marinella G Temprosa; Neil H White; Jill P Crandall Journal: J Clin Endocrinol Metab Date: 2016-02-22 Impact factor: 5.958
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Authors: Jolien de Jager; Adriaan Kooy; Philippe Lehert; Michiel G Wulffelé; Jan van der Kolk; Daniël Bets; Joop Verburg; Ab J M Donker; Coen D A Stehouwer Journal: BMJ Date: 2010-05-20
Authors: Annelies C Ham; Anke W Enneman; Suzanne C van Dijk; Sadaf Oliai Araghi; Karin M A Swart; Evelien Sohl; Janneke P van Wijngaarden; Nikita L van der Zwaluw; Elske M Brouwer-Brolsma; Rosalie A M Dhonukshe-Rutten; Natasja M van Schoor; Tischa J M van der Cammen; M Carola Zillikens; Robert de Jonge; Paul Lips; Lisette C P G M de Groot; Joyce B J van Meurs; André G Uitterlinden; Renger F Witkamp; Bruno H C Stricker; Nathalie van der Velde Journal: Drugs Aging Date: 2014-08 Impact factor: 3.923
Authors: Carlo Cappelli; Mario Rotondi; Ilenia Pirola; Barbara Agosti; Elena Gandossi; Umberto Valentini; Elvira De Martino; Antonio Cimino; Luca Chiovato; Enrico Agabiti-Rosei; Maurizio Castellano Journal: Diabetes Care Date: 2009-06-05 Impact factor: 19.112