Abstract
Peripheral neuropathy (PN) is a primary complication of type 2 diabetes mellitus (T2DM) and a direct manifestation of vitamin B12 deficiency. Examining the effects of metformin use on PN status became imperative following clinical studies that showed the vitamin B12-lowering effect of the medication. The complexity of the topic and the inconsistency of the results warrant consideration of topic-specific perspectives for better understanding of the available evidence and more appropriate design of future studies.
Highlights
type 2 diabetes mellitus (T2DM) is a metabolic disorder that is increasingly becoming a public health concern
Since vitamin B12 is essential for the remethylation of homocysteine to methionine, metformin-induced vitamin B12 deficiency could be associated with hyperhomocysteinemia, a condition with a questionable detrimental impact on macrovascular disease in T2DM patients [10]
The conflicting results of the available evidence reflect the complexity of linking metformin-induced vitamin B12 deficiency and Peripheral neuropathy (PN) in T2DM patients, where the disease state induces neuropathies
Summary
T2DM is a metabolic disorder that is increasingly becoming a public health concern. The disease is associated with a variety of systemic macrovascular and microvascular complications. 27% of diabetes-related medical costs are attributable to DPN [3] Both American and European guidelines recommend metformin as the first-line agent for the pharmacological management of T2DM. Recent American Diabetes Association (ADA) guidelines recommend periodic testing of vitamin B12 in metformin-treated patients, especially in those with peripheral neuropathy [9]. Since vitamin B12 is essential for the remethylation of homocysteine to methionine, metformin-induced vitamin B12 deficiency could be associated with hyperhomocysteinemia, a condition with a questionable detrimental impact on macrovascular disease in T2DM patients [10]. PN resulting from vitamin B12 deficiency is clinically indistinguishable from DPN [13] Such PN neuropathy can be asymptomatic [12] and could likely worsen DPN in diabetic patients. The potential for metformin-induced vitamin B12 deficiency to cause or worsen DPN has recently been investigated by several studies with conflicting findings. This article provides new perspectives that may assist in interpreting the available evidence and give a deeper understanding of the topic for the design of future research
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