Vitamin B 12 and homocysteine status during pregnancy in the metformin in gestational diabetes trial: responses to maternal metformin compared with insulin treatment

Aim The aim of the study is to compare the effects of metformin and insulin treatment for gestational diabetes mellitus ( GDM ) on vitamin B 12 and homocysteine (Hcy) status. Methods Women with GDM , who met criteria for insulin treatment, were randomly assigned to metformin (n = 89) or insulin (n = 91) in the Adelaide cohort of the metformin in gestational diabetes ( MiG ) trial. Fasting serum total vitamin B 12 ( TB 12 ), holotranscobalamin ( HoloTC ), a marker of functional B 12 status and plasma Hcy concentrations were measured at 20–34 weeks (at randomization) and 36 weeks gestation, then at 6–8 weeks postpartum. Results Circulating TB 12 , HoloTC and Hcy were similar in both treatment groups at each time point. Women who were taking dietary folate supplements at randomization had higher serum TB 12 and HoloTC at randomization than those not taking folate. Overall, serum TB 12 fell more between randomization and 36 weeks gestation in the metformin group than in the insulin group (metformin: −19.7 ± 4.7 pmol/l, insulin: −6.4 ± 3.6 pmol/l, p = 0.004). The decrease in serum TB 12 during treatment was greater with increasing treatment duration in metformin‐treated (p < 0.001), but not in insulin‐treated women. Conclusions Total, but not bioavailable, vitamin B 12 stores were depleted during pregnancy to a greater extent in metformin‐treated than in insulin‐treated women with GDM , but neither analyte differed between groups at any stage. This adds further evidence supporting metformin as a safe alternative treatment to insulin in GDM . Further investigation is needed to evaluate whether women treated with metformin for longer periods in pregnancy require additional B 12 or other supplementation.