An observational study of the effect of metformin on B12 status and peripheral neuropathy

Abstract

AimsMetformin is associated with lowering of vitamin B12 levels. We hypothesise that holotranscobalamin (holoTC) and methylmalonic acid (MMA) are more sensitive indicators of B12 deficiency in patients receiving metformin therapy, and that these correlate with declining peripheral neurological function. MethodsPatients with type 2 diabetes were recruited and divided into those receiving metformin for greater than 6 months and a non-metformin group. Baseline characteristics were measured in both groups including vitamin B12, holoTC and MMA concentrations. Neurological function was assessed using neurothesiometry, monofilament, Neuropathy Total Symptom Score-6 questionnaire and the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs questionnaire. ResultsIn total, 202 patients were recruited: 152 in the metformin group and 50 in the non-metformin group. Vitamin B12 levels were lower in the metformin group (219.1±105.4 ng/L, 281.4±95.1 ng/L, p<0.001). HoloTC was significantly lower in the metformin group (54.8±30.5 pmol/L, 70.1±26.0 pmol/L, p=0.002). No significant difference in serum MMA was observed between the two groups (0.40±0.26 μmol/L, 0.35±0.22, p=0.23). No significant difference in neurological function was observed between the groups. ConclusionAlthough metformin therapy is associated with lower vitamin B12 status there does not appear to be any significant effect on peripheral neuropathy in those receiving metformin. We do not recommend changing current practice to routinely monitor or replace patients receiving metformin with vitamin B12 unless clinically indicated. Br J Diabetes Vasc Dis 2012;12:189-193.

Association of Vitamin B12 and Metformin in Type II Diabetes Patients in Bahrain

“…Similar to our study the result of another study published in 2016 could not establish any association with the presence of diabetic peripheral neuropathy in T2DM patients and use of metformin [16]. Similar observation was reported from a study comparing metformin user and nonuser diabetic patients [17]. There was no difference in neurological function between the both groups.…”

“…Similar to their observation, Ting et al [21] demonstrated that Vitamin B 12 deficiency has significant association with metformin use of 3 years or more the adjusted odds ratio was (2.39, 95% confidence interval, 1.46-3.91) (P=0.001). Contrary to all these observations, Chen et al [17] did not find any significant association between metformin duration and vitamin B 12 deficiency. In our study when we compared vitamin B 12 deficient and normal patients receiving metformin for less than1 year,1-5 years, 6-10 years, 11-20 years and longer than 20 years.…”

Impact of type 2 Diabetes and Metformin use on Vitamin B12 Associated Biomarkers - an Observational Study

“…VB12, HoloTc or Hcy levels did not differ in patients with mild, moderate or severe symptoms of neuropathy assessed with the NSS and NDS, while, well-established risk factors such as age and duration of diabetes differed between groups. While some studies showed associations between neuropathy, VB12 associated biomarkers, and metformin use [8,42], others failed to find such correlations [43][44][45], making results controversial, overall. Controversy might exist because a range of different assessments for neuropathy and differences in study designs exist.…”

Metformin and Vitamin B12 Deficiency: Where Do We Stand?

“…The study also reported a correlation between the cumulative dose of the medication and the MMA levels for the first time. However, a British cross-sectional study found no statistically significant differences in MMA concentrations between the users and non-users of metformin (104). A randomized controlled trial in Norway also reported no metformin effect on MMA in women with polycystic ovary syndrome treated with the medication for 16 weeks (93).…”