Effect of metformin therapy on vitamin D level in patients with type 2 diabetes mellitus

Main Article Content

K.O. Masliy


Background. Recent studies have shown that patients with diabetes mellitus (DM) often have skeletal disorders, in particular, reduced bone mineral density, osteoporosis. Apart from the disease itself, the nature of hypoglycemic therapy can make a significant contribution to increasing the risk of diabetes mellitus. The aim of the study was to evaluate the effect of metformin on the serum vitamin D level in patients with type 2 DM. Materials and methods. There were 47 patients under observation. The main group (n = 25) included patients who suffered from type 2 DM and received treatment with metformin, a hypoglycemic drug. The control group consisted of apparently healthy persons (n = 22). The study excludes patients with pathology of parathyroid glands, thyroid function disorders, kidney disease, and those taking vitamin D or calcium. Le­vels of 25­hydroxyvitamin D (25(OH)D), parathormone, ioni­zed calcium, glycated hemoglobin (HbA1c) were evaluated. Results. Forty­seven patients aged 42 to 69 years (average age 58.0 ± 17.5 years) were examined. A study of serum 25(OH)D level showed that in most patients it was low. The average level of 25(OH)D in the main group was 18.37 ± 7.62 ng/ml (5.89–32.8 ng/ml). The study showed a higher prevalence of vitamin D deficiency among patients with type 2 DM (66.7 %) receiving metformin than in the control group (7.69 %). It was found that vitamin D levels were lower in patients with poorer glycemic control of type 2 DM (HbA1c > 7 %) — 15.03 ± 7.60 ng/ml and 22.75 ± 7.62 ng/ml, respectively. Conclusions. The study showed a higher prevalence of vitamin D deficiency among patients with type 2 DM (66.7 %) receiving metformin than in the control group (7.69 %). A reliable inverse correlation was found between the elevated HbA1c level and reduced 25(OH)D content. The level of 25(OH)D was significantly lower in the main group of patients receiving metformin therapy compared to the control group.

Article Details

How to Cite
Masliy, K. “Effect of Metformin Therapy on Vitamin D Level in Patients With Type 2 Diabetes Mellitus”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 15, no. 2, May 2019, pp. 133-7, doi:10.22141/2224-0721.15.2.2019.166105.
Original Researches


Kurra S, Siris E. Diabetes and bone health: the relationship between diabetes and osteoporosis-associated fractures. Diabetes Metab Res Rev. 2011 Jul;27(5):430-5. doi: 10.1002/dmrr.1197.

International Diabetes Federation. IDF Diabetes Atlas, 8th ed. Brussels, Belgium: International Diabetes Federation; 2017.

Kyryliuk ML, Shchekaturova LV, Atanova YaO. Bone mineral density in women in postmenopausal period with type 2 diabetes mellitus. Clinical Endocrinology and Endocrine Surgery. 2017;(1):63-70. (in Ukrainian).

Pankiv V, Pankiv I. Association of vitamin D status with body mass index in adolescents in Ukraine. Rom J Diabetes Nutr Metab Dis. 25(4):377-381. doi: 10.2478/rjdnmd-2018-0045.

Hernlund E, Svedbom A, Ivergård M, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8:136. doi: 10.1007/s11657-013-0136-1.

Napoli N, Strotmeyer ES, Ensrud KE, et al. Fracture risk in diabetic elderly men: the MrOS study. Diabetologia. 2014 Oct;57(10):2057-65. doi: 10.1007/s00125-014-3289-6.

Oei L, Zillikens MC, Dehghan A, et al. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control the Rotterdam Study. Diabetes Care. 2013 Jun;36(6):1619-28. doi: 10.2337/dc12-1188.

Patsch JM, Kiefer FW, Varga P, et al. Increased bone resorption and impaired bone microarchitecture in short-term and extended high-fat dietinduced obesity. Metabolism. 2011 Feb;60(2):243-9. doi: 10.1016/j.metabol.2009.11.023.

Bolinder J, Ljunggren O, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014 Feb;16(2):159-69. doi: 10.1111/dom.12189.

Ruderman NB, Carling D, Prentki M, Cacicedo JM. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest. 2013 Jul;123(7):2764-72. doi: 10.1172/JCI67227.

Vestergaard P, Rejnmark L, Mosekilde L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia. 2005 Jul;48(7):1292-9. doi: 10.1007/s00125-005-1786-3.

Hegazy SK. Evaluation of the anti-osteoporotic effects of metformin and sitagliptin in postmenopausal diabetic women. J Bone Miner Metab. 2015 Mar;33(2):207-12. doi: 10.1007/s00774-014-0581-y.

Zinman B, Haffner SM, Herman WH, et al. Effect of rosiglitazone, metformin, and glyburide on bone biomarkers in patients with type 2 diabetes. J Clin Endocrinol Metab. 2010 Jan;95(1):134-42. doi: 10.1210/jc.2009-0572.

Borges J, Bilezikian J, Jones-Leone A, et al. A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 diabetes mellitus patients. Diabetes Obes Metab. 2011 Nov;13(11):1036-46. doi: 10.1111/j.1463-1326.2011.01461.x.

Kanazawa I, Yamaguchi T, Yano S, Yamauchi M, Sugimoto T. Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression. Biochem Biophys Res Commun. 2008 Oct 24;375(3):414-9. doi: 10.1016/j.bbrc.2008.08.034.

Hegazy SK. Evaluation of the anti-osteoporotic effects of metformin and sitagliptin in postmenopausal diabetic women. J Bone Miner Metab. 2015 Mar;33(2):207-12. doi: 10.1007/s00774-014-0581-y.

Out M, Top WMC, Lehert P, Schalkwijk CA, Stehouwer CDA, Kooy A. Long-term treatment with metformin in type 2 diabetes and vitamin D levels: A post-hoc analysis of a randomized placebo-controlled trial. Diabetes Obes Metab. 2018;20(8):1951-1956. doi: 10.1111/dom.13327.

Kos E, Liszek MJ, Emanuele MA, Durazo-Arvizu R, Camacho P. Effect of metformin therapy on vitamin D and vitamin B12 levels in patients with type 2 diabetes mellitus. Endocr Pract. 2012;18(2):179-84. doi: 10.4158/EP11009.OR.

Yefimov AS, Mikhalchuk LM. Vitamin D Deficiency and Vascular Lesions in Diabetes Mellitus Type 2. Mìžnarodnij endokrinologìčnij žurnal. 2013;(53):10-14. (in Ukrainian).