Therefore , although the overall effect of metformin on the concentration of serum Hcy was neutral , our results suggested that metformin could increase the concentration of Hcy when exogenous B-group vitamins or folic acid supplementation was not given
The aim of this systematic review is to assess whether metformin could change the concentration of serum homocysteine ( Hcy ) with and without simultaneous supplementation of B-group vitamins or folic acid .
Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial
Objectives To study the effects of metformin on the incidence of vitamin B-12 deficiency ( < 150 pmol/l ) , low concentrations of vitamin B-12 ( 150 - 220 pmol/l ) , and folate and homocysteine concentrations in patients with type 2 diabetes receiving treatment with insulin . Design Multicentre r and omised placebo controlled trial . Setting Outpatient clinics of three non-academic hospitals in the Netherl and s. Participants 390 patients with type 2 diabetes receiving treatment with insulin . Intervention 850 mg metformin or placebo three times a day for 4.3 years . Main outcome measures Percentage change in vitamin B-12 , folate , and homocysteine concentrations from baseline at4 , 17 , 30 , 43 , and 52 months . Results Compared with placebo , metformin treatment was associated with a mean decrease in vitamin B-12 concentration of −19 % ( 95 % confidence interval −24 % to −14 % ; P<0.001 ) and in folate concentration of −5 % ( 95 % CI −10 % to −0.4 % ; P=0.033 ) , and an increase in homocysteine concentration of 5 % ( 95 % CI −1 % to 11 % ; P=0.091 ) . After adjustment for body mass index and smoking , no significant effect of metformin  on folate concentrations was found . The absolute risk of vitamin B-12 deficiency ( < 150 pmol/l ) at study end was 7.2 percentage points higher in the metformin group than in the placebo group ( 95 % CI 2.3 to 12.1 ; P=0.004 ) , with a number needed to harm of 13.8 per 4.3 years ( 95 % CI 43.5 to 8.3 ) . The absolute risk of low vitamin B-12 concentration ( 150 - 220 pmol/l ) at study end was 11.2 percentage points higher in the metformin group ( 95 % CI 4.6 to 17.9 ; P=0.001 ) , with a number needed to harm of 8.9 per 4.3 years ( 95 % CI 21.7 to 5.6 ) . Patients with vitamin B-12 deficiency at study end had a mean homocysteine level of 23.7 µmol/l ( 95 % CI 18.8 to 30.0 µmol/l ) , compared with a mean homocysteine level of 18.1 µmol/l ( 95 % CI 16.7 to 19.6 µmol/l ; P=0.003 ) for patients with a low vitamin B-12 concentration and 14.9 µmol/l ( 95 % CI 14.3 to 15.5 µmol/l ; P<0.001 compared with vitamin B-12 deficiency ; P=0.005 compared with low vitamin B-12 ) for patients with a normal vitamin B-12 concentration ( > 220 pmol/l ) . Conclusions Long term treatment with metformin increases the risk of vitamin B-12 deficiency , which results in raised homocysteine concentrations . Vitamin B-12 deficiency is preventable ; therefore , our findings suggest that regular measurement of vitamin B-12 concentrations during long term metformin treatment should be strongly considered . Trial registration Clinical trials.gov NCT00375388
Therefore , although the overall effect of metformin on the concentration of serum Hcy was neutral , our results suggested that metformin could increase the concentration of Hcy when exogenous B-group vitamins or folic acid supplementation was not given
The aim of this systematic review is to assess whether metformin could change the concentration of serum homocysteine ( Hcy ) with and without simultaneous supplementation of B-group vitamins or folic acid .