BACKGROUND : The association between long-term metformin use and low vitamin B12 levels has been proven.
However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation
among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes
mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate:
1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12
and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients.
METHODS : In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of
two public hospitals in South Africa were approached for participation. Participation included measuring vitamin
B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire.
The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with
NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and
peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple
logistic regression was used to determine risk factors for vitamin B12 deficiency.
RESULTS : Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in
presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209).
Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman’s rho =0.056, P = 0.54). HbA1c (mmol/mol)
(OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk
factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline
significance (OR = 1.96, 95 % CI: 0.99 to 3.88, P = 0.053).
CONCLUSIONS : Close to third of metformin-treated T2DM patients had vitamin B12 deficiency. The deficiency was
not associated with peripheral neuropathy. Black race was a protective factor for vitamin B12 deficiency.