Long-term metformin treatment may up risk of peripheral neuropathy

Among older adults, exposure to at least 18 months of metformin carries a two-to-three times increased likelihood of developing peripheral neuropathy, a study has found.

The study used data from the Veterans Affairs registry and included 210,004 individuals (mean age, 66.2 years; 96 percent male) prescribed metformin for 47.0 months. Most of them were past or current smokers (79 percent), but only 9 percent had a history of alcohol abuse.

During the study duration, 58.8 percent of the participants underwent a serum vitamin B12 assessment, of which 3.0 percent were deficient, 20.5 percent were borderline low, and 76.5 were adequate. After at least 6 months of metformin prescription, only 27.8 percent received vitamin B12 supplementation.

Peripheral neuropathy occurred in 19.3 percent of patients after an average of 28.1 months after metformin initiation. This group of patients was exposed to metformin longer (average, 59.2 vs 44.1 months) and were younger (average, 65.8 vs 66.3 years).

Multivariable logistic regression analysis showed that the duration of metformin treatment was associated with greater odds of developing peripheral neuropathy. The adjusted odds ratios relative to 6 to <18 months of treatment were 1.57 (95 percent confidence interval [CI], 1.51–1.63) with 18 to <44.1 months of treatment, 2.05 (95 percent CI, 1.97–2.14) with 44.1 to <61 months, 2.69 (95 percent CI, 2.58–2.79) with ≥61 months (p<0.0001 for all).

Additional studies are needed to establish whether the association may be due to a decline in vitamin B12 levels following metformin initiation.