Effect of Metformin on Plasma Homocysteine, Vitamin B12 and Folic Acid: a Cross-Sectional Study in Patients with Type 2 Diabetes Mellitus
Manat Pongchaidecha BPharm, PhD*, Vinida Srikusalanukul BPharm, MSc**, Apisit Chattananon BPharm, MPPM*** , Sompong Tanjariyaporn MD****
Affiliation : * Department of Pharmaceutics (Clinical Pharmacy), Faculty of Pharmacy, Silpakorn University ** Pharmacy Unit, Makaruk Hospital, Ta Maka, Kanchanaburi *** Professional Relation and Educational Support, Diethelm Trading Ltd. **** Medical Unit, Makaruk Hospital, Ta Maka, Kanchanaburi
Objective : To determine the effect of metformin on the levels of plasma homocysteine (Hcy), serum vitamin B12
and folic acid in patients with type 2 diabetes mellitus and the relationship between cumulative metformin
exposure and levels of plasma homocysteine (Hcy).
Materials and Methods : The cross sectional study was conducted to assess the effect of metformin treatment on
plasma homocysteine (Hcy), serum vitamin B12 and folic acid in 152 type 2 diabetic out-patients aged
between 35-65 years old at the Diabetes Clinic of The Makaruk Hospital, Kanchanaburi, Thailand. Among
those, 88 and 64 patients were categorised to the metformin and non-metformin group according to their
records of receiving metformin treatment for a period of a minimal 6 consecutive months before the study.
Fasting blood was drawn from each patient and analysed for plasma homocysteine using the Fluorescence
Polarization Immunoassay (FPIA) method (IMX Analyzer), and serum vitamin B12 and folic acid using the
radioimmunoassay method.
Results : The plasma Hcy levels showed no significant difference (p = 0.544) among patients in the metformin
group compared with those in the non-metformin group (10.6+5.8 mol/L vs 10.4 + 4.0 mol/L). There was a
significant difference (p = 0.011) in the levels of serum vitamin B12 among patients in the metformin group
and among those in the non-metformin group (318.0 + 192.2 pg/mL vs 434.3 + 300.7 pg/mL). However, there
was no significant difference (p = 0.090) in serum folic acid levels between patients in the metformin and
those in the non-metformin group (8.8 + 5.1 ng/mL vs 7.7 + 3.8 ng/mL). The plasma Hcy levels showed a
significant correlation with the duration of metformin treatment (p = 0.014) and the amount of metformin
received (p = 0.015) with the Spearman correlation coefficient of 0.260 and 0.258 respectively.
Conclusion : Even though the direct effect of metformin treatment on the plasma Hcy could not be concluded
from the present study, it was found that there was a significant depletion of level of serum vitamin B12 among
patients who had been on long-term metformin treatment. Therefore, vitamin B12 supplement is suggested for
diabetic patients who are receiving metformin medication.
Keywords : Metformin, Homocysteine, Vitamin B12, Folic Acid, Diabetes Mellitus
