ADA: Deficiency in Vitamin B12 with Metformin Linked to Neuropathy

Metformin use has been previously shown to be associated with vitamin B₁₂ deficiency. Peripheral neuropathy is typically diagnosed as diabetic neuropathy, but this can also be a symptom of vitamin B₁₂ deficiency.

Jasna Klen, PhD, an internist, radiologist, and diabetes specialist at Hospital Trbovlje in Slovenia, who presented the research stated that, "We had a few patients complaining about peripheral neuropathy who hadn't [had diabetes] very long, but they were on metformin. We decided to look at vitamin B₁₂ deficiency."

The study involved 84 patients with type 2 diabetes who had been on metformin for at least 4 years. Mean age was 63 years and mean body mass index was 32.1 kg/m².

The researchers measured serum vitamin B₁₂ concentrations to determine whether there was an association with peripheral neuropathy. Deficiency was defined as a serum concentration of 150 pmol/L or less; borderline deficiency was defined as a concentration from 150 to 250 pmol/L.

Fifteen patients (17.8%) met the threshold for vitamin B₁₂ deficiency and 22 (26%) for borderline deficiency. Vitamin B₁₂ levels were found to be negatively associated with age (P = .035) and duration of metformin use (P = .048). Lower serum levels of vitamin B₁₂ were associated with more severe peripheral neuropathy (P = .002).

Dr. Klen stated that, "I think we must be careful about older patients and patients who take metformin for a long time. We must measure levels of vitamin B₁₂. We don't change therapies [at our institution], but we treat deficiencies with B₁₂ supplements."

According to Carol Wysham, MD, clinical professor of medicine at the University of Washington and section head of the Rockwood Center of Diabetes and Endocrinology in Spokane, "It has been known for some time that patients on metformin have impaired vitamin B₁₂ absorption, but the clinical relevance had not been determined." Now that we know vitamin B₁₂ deficiency is clinically relevant, "What I'd really like to see is a study suggesting the best replacement. You can supplement, but how much? Over-the-counter supplements have way more B₁₂ than you need, so do you give them once a week? Nobody is giving us guidance," Dr. Wysham added.

Abstract 954-P. American Diabetes Association (ADA) 72nd Scientific Sessions Presented June 9, 2012.