Effect of Metformin Therapy on Vitamin D and Vitamin B12 Levels in Patients with Type 2 Diabetes Mellitus



      To determine the effect of metformin on 25-hydroxyvitamin D [25(OH)D] and vitamin B12 levels in patients with type 2 diabetes mellitus.


      We performed a retrospective review of medical records of patients treated between 2003 and 2009 at Loyola University Medical Center, Maywood, Illinois, in both ambulatory primary care and endocrinology clinics. The study cohort consisted of 706 patients with type 2 diabetes mellitus who were 20 to 93 years old (mean age, 63 ± 13) and had a mean body mass index of 33.1 kg/m2. Of these patients, 42% were treated with metformin, and 34% had been diagnosed with osteoporosis or osteopenia.


      Patients taking metformin had statistically significant lower vitamin B12 levels than those not receiving metformin (P < .0001; 95% confidence interval [CI] = −220 to −84 pg/mL). No statistically significant difference was found between users and nonusers of metformin in regard to 25(OH)D levels when adjusted for variables (P = .297; 95% CI for mean difference = −0.7 to 2.2 ng/mL). Metformin use did not adversely affect successful treatment of vitamin D deficiency in this patient population as a whole, nor did it affect the subgroup with osteoporosis (P = .956). The patients with osteoporosis had statistically significant lower baseline 25(OH)D levels in comparison with those without osteoporosis, when adjustments were made for all variables (P = .003; 95% CI = 0.7 to 3.5 ng/ mL).


      This study confirms the higher prevalence of vitamin B12 deficiency in metformin-treated patients with type 2 diabetes than in those not treated with metformin. This study also suggests that vitamin D deficiency is not a clinical concern among metformin-treated patients with type 2 diabetes and that metformin does not negatively affect treatment of vitamin D deficiency in these patients. (Endocr Pract. 2012;18:179–184)
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      1. National Diabetes Information Clearinghouse (NDIC). National Diabetes Statistics, 2011. NIH publication no. 11-3892, February 2011. http://diabetes.niddk.nih.gov/dm/pubs/statistics/

        • Nathan D.M.
        • Buse J.B.
        • Davidson M.B.
        • 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 [published correction appears in Diabetes Care. 200629:2816-2818].
        Diabetes Care. 2006; 29: 1963-1972
        • Ting R.Z.
        • Szeto C.C.
        • Chan M.H.
        • Ma K.K.
        • Chow K.M.
        Risk factors of vitamin B12 deficiency in patients receiving metformin.
        Arch Intern Med. 2006; 166: 1975-1979
        • Tomkin G.H.
        • Hadden D.R.
        • Weaver J.A.
        • Montgomery D.A.
        Vitamin B12 status of patients on long-term metformin therapy.
        Br Med J. 1971; 2: 685-687
        • Adams J.F.
        • Clark J.S.
        • Ireland J.T.
        • Kesson C.M.
        • Watson W.S.
        Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy.
        Diabetologia. 1983; 24: 16-18
        • Bauman W.A.
        • Shaw S.
        • Jayatilieke E.
        • Spungen A.M.
        • Herbert V.
        Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin.
        Diabetes Care. 2000; 23: 1227-1231
        • Wulffelé M.G.
        • Kooy A.
        • Lehert P.
        • 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: 455-463
        • De Jager J.
        • Kooy A.
        • Lehert P.
        • et al.
        Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial.
        BMJ. 2010; 340: c2181
        • Pittas A.G.
        • Lau J.
        • Hu F.B.
        • Dawson-Hughes B.
        The role of vitamin D and calcium in type 2 diabetes: a systemic review and meta-analysis.
        J Clin Endocrinol Metab. 2007; 92: 2017-2029
        • Chiu K.C.
        • Chu A.
        • Go V.L.
        • Saad M.F.
        Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction.
        Am J Clin Nutr. 2004; 79: 820-825
      2. National Institutes of Health (NIH) Office of Dietary Supplements. Dietary supplement fact sheet: vitamin D. http://ods.od.nih.gov/factsheets/VitaminD_pf.asp