Metformin-induced Vitamin B12 Deficiency Presenting as a Peripheral Neuropathy

David S.H. Bell, MD


South Med J. 2010;103(3):265-267. 

In This Article

Abstract and Introduction


Chronic metformin use results in vitamin B12 deficiency in 30% of patients. Exhaustion of vitamin B12 stores usually occurs after twelve to fifteen years of absolute vitamin B12 deficiency. Metformin has been available in the United States for approximately fifteen years. Vitamin B12 deficiency, which may present without anemia and as a peripheral neuropathy, is often misdiagnosed as diabetic neuropathy, although the clinical findings are usually different. Failure to diagnose the cause of the neuropathy will result in progression of central and/or peripheral neuronal damage which can be arrested but not reversed with vitamin B12 replacement. To my knowledge, this is the first report of metformin-induced vitamin B12 deficiency causing neuropathy.


Metformin is now recommended as initial therapy for type 2 diabetes.[1] Because of this, metformin used either as monotherapy or in combination with other antidiabetic oral agents and insulin has become the most widely utilized antidiabetic oral agent.

Metformin's best known and most feared side effect, ie lactic acidosis almost never occurs if metformin is not used inappropriately.[2] The common side effects of metformin are gastrointestinal and can be overcome by initiating metformin therapy at a lower dose and slowly increasing the dose, by giving metformin after meals, or by utilizing a slow-release metformin preparation.[3]

However, a common, potentially damaging, and well-documented complication of metformin—vitamin B12 malabsorption—is poorly recognized and not screened for or treated prophylactically by the majority of physicians who prescribe metformin. This is unfortunate since a correctable cause of irreversible damage to the central and peripheral nervous system may be overlooked. In this article, I present a case of peripheral neuropathy that could have been avoided by the monitoring of vitamin B12 levels or by prophylactic annual vitamin B12 injections. Furthermore, at presentation the neuropathic symptoms and clinical findings could have been misdiagnosed as being due to diabetic neuropathy, which would have further prolonged the time to diagnosis and treatment of the neuropathy and resulted in further neurological damage.


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