Which treatments contribute to vitamin B12 deficiency in type 2 diabetic patients?

This study examined the effect of sulfonylurea or insulin treatment, as well as metformin (Glucophage), on vitamin B₁₂ deficiency in patients with type 2 diabetes.

The initial drug treatment for newly diagnosed type 2 diabetes patients is metformin, which increases sensitivity to insulin (the hormone necessary for breaking down the glucose [sugar] taken in from food) and decreases the amount of glucose produced by the liver. However, type 2 diabetes is a progressive disease and other treatments are eventually needed to control blood glucose levels. Insulin replacement and sulfonylureas (drugs that increase insulin production by the body) are often added to metformin therapy.

Vitamin B₁₂ is essential for the normal functioning of the brain and nervous system, and deficiencies can lead to neurological symptoms such as numbness and impaired vibration sensation. Because peripheral neuropathy (damage to nerves in the arms and legs) is a complication of diabetes, the symptoms of vitamin B₁₂ deficiency are often misdiagnosed. Long-term use of metformin has been associated with deficiencies in vitamin B₁₂, but it is not clear whether combination of metformin and other treatments, such as insulin or sulfonylureas, increases the problem.

The current study examined the effect of sulfonylureas (such as, gliclazide [Diamicron] and glibenclamide [Daonil]) and insulin, used in conjunction with metformin, on vitamin B₁₂ deficiency. 394 patients with established type 2 diabetes, who were treated either with an insulin/metformin combination or a sulfonylurea/metformin combination were included in the study. The medication history of each patient was determined through a questionnaire, and levels of vitamin B₁₂ were measured through a blood test.

In total, 56 patients (14.2%) were determined to be deficient in vitamin B₁₂. The average vitamin B₁₂ level was significantly lower in the sulfonylurea group (600 pg/mL) compared to the insulin group (757.7 pg/mL). Sulfonylurea use increased the risk of vitamin B₁₂ deficiency by 4.75-fold. 17.4% of patients in the sulfonylurea group were vitamin B₁₂ deficient, compared to only 4.2% in the insulin group. Rates of anemia (low red blood cell levels) were higher in patients with vitamin B₁₂ deficiency (26.8%) compared to patients without vitamin B₁₂ deficiency (13.6%).

Longer duration of metformin treatment and higher doses of metformin also increased the risk of vitamin B₁₂ deficiency. Patients treated with metformin for more than ten years had 6.7-fold higher risk of vitamin B₁₂ deficiency and patients receiving more than 2000 mg/day had 31.2-fold higher risk of vitamin B₁₂ deficiency.

This study concluded that the combined treatments of sulfonylureas and metformin increased the risk of vitamin B₁₂ deficiency in type 2 diabetic patients. 

Consult with your doctor if you are worried about developing vitamin B₁₂ deficiency.