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 B-12 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, Delta(4)-androstenedione, and DHEA-S were higher. No differences were observed in the HOMA-IR, SHBG, hemoglobin, HbA1c, vitamin B-12, or serum 25(OH)D-3 concentrations between groups. Among those on MET, 17.4% exhibited vitamin B-12 deficiency, whereas none of the controls had low vitamin B-12 concentrations. Participants on MET therapy consumed less energy concerning their requirements, less vitamin B-12, 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 B-12. The results suggest that, in children and adolescents on MET therapy, the dietary intake of vitamin B-12 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 B-12 concentrations. Thus, caution is required when prescribing MET in children and adolescents, and replacement is warranted.

Automated summary

The International Society of Pediatric and Adolescent Diabetes (ISPAD) recommends the use of metformin (MET) for metabolic disturbances and hyperglycemia in children and adolescents. However, a potential concern of MET therapy is vitamin B-12 deficiency, which has mainly been observed in studies conducted on adults. In this case-control study, it was found that children and adolescents on MET therapy had suboptimal intake of vitamin B-12 and may experience synergistic reduction in circulating vitamin B-12 concentrations when paired with MET. Therefore, caution is needed when prescribing MET for this age group and vitamin B-12 replacement may be necessary.