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17-01-2010 | Diabetes | Article

Metformin exposure could worsen diabetic neuropathy


Free abstract

MedWire News: Exposure to metformin may inadvertently cause worsening of peripheral neuropathy in patients with Type 2 diabetes, say researchers.

“Long-term use of metformin is associated with malabsorption of vitamin B12 (cobalamin [Cbl]), and elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, which may have deleterious effects on peripheral nerves,” explain Daryl Wile and Cory Toth from the University of Calgary in Alberta, Canada.

To clarify the effect of long-term metformin treatment on the symptoms of diabetic peripheral neuropathy, the team carried out a prospective case-control study involving 59 Type 2 diabetic patients with peripheral neuropathy who had been treated with metformin for over 6 months and 63 similar patients who had not been treated with metformin (controls).

The authors used the Toronto Clinical Scoring System and Neuropathy Impairment Score (TCSS), as well as electrophysiological measures to assess the degree of neuropathy. They also measured concentrations of Cbl, Hcy, and MMA to assess their potential impact.

Writing in the journal Diabetes Care, Wile and Toth report that the metformin-treated patients had significantly lower concentrations of Cbl than controls, at a median of 231 versus 486 pmol/l.

In contrast, median Hcy and MMA were significantly higher in the metformin-treated group compared with controls, at 11.6 versus 8.4 µmol/l and 0.18 versus 0.11 µmol/l, respectively.

The TCSS and electrophysiological measures used to assess the degree of neuropathy showed that metformin-treated patients had significantly more severe peripheral neuropathy than controls (TCSS score of 10 vs 5).

The authors note that “the cumulative metformin dose correlated strongly with these clinical and paraclinical group differences.”

They conclude: “The current findings suggest an association among metformin, elevated Cbl metabolites, and exacerbation of diabetic peripheral neuropathy, but further work is needed to prove a direct causal relationship and its mechanism.”

The researchers add: “Recognition of this readily identifiable and potentially treatable component of disease might improve quality of life for this large population of diabetic patients.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Helen Albert