Metformin-induced vitamin B12 deficiency: An underdiagnosed cause of diabetic neuropathy

Abstract

Metformin-induced vitamin B12 deficiency is a prevalent condition among patients with type 2 diabetes mellitus. In recent years, a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset, progression, and worsening of diabetic neuropathy (DNP) as well as its improvement with supplementation in cases of deficiency. Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measurement and supplementation, and some guidelines do not address it at all. Given that vitamin B12 therapy is an economical, safe, and widely available treatment in most countries and supported by emerging evidence of its potential benefits, greater efforts should be made to promote systematic screening for vitamin B12 deficiency in all patients with DNP before establishing a definitive diagnosis as well as in patients with diabetes with risk factors for deficiency. Vitamin B12 deficiency should be treated in all affected patients, and supplementation should be considered in those with borderline levels when confirmatory diagnostic tests for deficiency are unavailable. Clinical guidelines should place greater emphasis on the recommendations for measuring and supplementing vitamin B12 in these patients.

Keywords: Clinical guidelines; Diabetic neuropathy; Metformin; Type 2 diabetes mellitus; Vitamin B12 deficiency.

Figure 1

Folate and methionine cycles. BHMT: Betaine-homocysteine methyltransferase; SAM: S-adenosyl methionine; SAH: S-adenosyl homocysteine.