Vitamin B12 Deficiency With Metformin Linked to Neuropathy

Jim Kling

June 15, 2012

June 15, 2012 (Philadelphia, Pennsylvania) — In patients with type 2 diabetes taking metformin, vitamin B12 deficiency is associated with higher levels of peripheral neuropathy, according to a study presented here at the American Diabetes Association 72nd Scientific Sessions.

Chronic 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.

"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 [as an explanation], said Jasna Klen, PhD, an internist, radiologist, and diabetes specialist at Hospital Trbovlje in Slovenia, who presented the research.

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).

"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," said Dr. Klen.

It has been known for some time that patients on metformin have impaired vitamin B12 absorption, but the clinical relevance had not been determined, according to Carol Wysham, MD, clinical professor of medicine at the University of Washington in Seattle and section head of the Rockwood Center of Diabetes and Endocrinology in Spokane.

This study suggested that the 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 [on that]," Dr. Wysham told Medscape Medical News.

Dr. Klen has disclosed no relevant financial relationships. Dr. Wysham reports being on the speaker's bureau for Amylin Pharmaceuticals.

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


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