Serum Concentrations and Dietary Intake of Vitamin B₁₂ in Children and Adolescents on Metformin: A Case-Control Study

The International Society of Pediatric and Adolescent Diabetes (ISPAD) recommends metformin (MET) use for metabolic disturbances and hyperglycemia, either in combination with insulin therapy or alone. A caveat of MET therapy has been suggested to be biochemical vitamin B₁₂ deficiency, as seen mainly in studies conducted in adults. In the present case-control study, children and adolescents of different weight status tiers on MET therapy for a median of 17 months formed the cases group (n = 23) and were compared with their peers not taking MET (n = 46). Anthropometry, dietary intake, and blood assays were recorded for both groups. MET group members were older, heavier, and taller compared with the controls, although BMI z-scores did not differ. In parallel, blood phosphorus and alkaline phosphatase (ALP) concentrations were lower in the MET group, whereas MCV, Δ₄-androstenedione, and DHEA-S were higher. No differences were observed in the HOMA-IR, SHBG, hemoglobin, HbA1c, vitamin B₁₂, or serum 25(OH)D₃ concentrations between groups. Among those on MET, 17.4% exhibited vitamin B₁₂ deficiency, whereas none of the controls had low vitamin B₁₂ concentrations. Participants on MET therapy consumed less energy concerning their requirements, less vitamin B₁₂, more carbohydrates (as a percentage of the energy intake), and fewer fats (including saturated and trans fats) compared with their peers not on MET. None of the children received oral nutrient supplements with vitamin B₁₂. The results suggest that, in children and adolescents on MET therapy, the dietary intake of vitamin B₁₂ is suboptimal, with the median coverage reaching 54% of the age- and sex-specific recommended daily allowance. This low dietary intake, paired with MET, may act synergistically in reducing the circulating vitamin B₁₂ concentrations. Thus, caution is required when prescribing MET in children and adolescents, and replacement is warranted.