Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and the leading cause of diabetic foot, lower limb amputations, and disabling neuralgia. DPN affects 30-50% of patients with diabetes.
Metformin is one of the most widely used oral hypoglycemic agents for treating type 2 diabetes. However, treatment with metformin is associated with vitamin B12 deficiency and can lead to irreversible damage to the nervous system and increase the risk of DPN.
Metformin Dose-Dependently Increases The Risk of Diabetic Peripheral Neuropathy
Chinese scientists evaluated the relationship between metformin treatment and the risk of DPN in patients with type 2 diabetes (T2D). The study included data from 37,052 T2D patients taking metformin and 12,653 not taking metformin. The mean follow-up time for patients was 6 years.
Patients were grouped according to their metformin dose:
- No metformin;
- Low doses – metformin <1.0 g/day;
- Moderate amounts – 1.0-2.0 g/day;
- High doses – >2.0 g/day.
Metformin treatment increased the risk of DPN by 84%. The risk increased with high doses of metformin:
- Median amounts increased the risk of diabetic peripheral neuropathy (DPN) by 1.53 times;
- High doses increased the risk by 4.31 times;
- Low doses did not affect the risk of DPN.
In addition, patients receiving metformin had a higher long-term risk of DPN (>2 years of observation) than those without metformin. The highest risk was in the high-dose group.
Metformin treatment was also associated with a higher risk of DPN in patients under 60 who visited the doctor less frequently, had fewer comorbidities, and did not take antihypertensive and hypolipidemic drugs.
Taking Vitamin B12 Protects against Diabetic Peripheral Neuropathy
Vitamin B12 (cobalamin) is a water-soluble vitamin found in animal products. Vitamin B12 is necessary for DNA synthesis and neuroprotection. B12 deficiency can lead to anemia, progressive demyelination, and peripheral neuropathy.
The use of metformin leads to a significant decrease in vitamin B12 concentration and increases the risk of B12 deficiency in patients with diabetes. An increase of 1 mg daily metformin dose is associated with a decrease in vitamin B12 concentration of 0.042 pmol/L.
In this study, taking vitamin B12 prevented the increase in the risk of DPN in patients who were taking metformin.
Conclusion
Long-term use of metformin may lead to a deficiency in vitamin B12 in the blood serum. B12 deficiency can contribute to peripheral nerve damage.
The use of metformin increases the risk of diabetic peripheral neuropathy (DPN) by 84%. High doses of metformin (>2.0 g/day) increase the risk of DPN by more than 4 times.
The risk of DPN from taking metformin increases in patients under 60 years old. Therefore, it is essential to use caution when prescribing metformin in the early stages of diabetes to prevent peripheral neuropathy in patients with mild symptoms.
Taking vitamin B12 supplements may prevent the development and progression of DPN.
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