Metformin and Vitamin B12 Deficiency: Evidence of Progressive Decline With Higher Dose and Longer Duration
DOI:
https://doi.org/10.64149/J.Ver.8.18s.1-9Keywords:
Metformin; Vitamin B12 deficiency; Type 2 diabetes mellitus; Dose-response; Duration-response; Correlation analysis; Macrocytosis; Peripheral smear; Hypersegmented neutrophils..Abstract
Background: Metformin is the first-line therapy for type 2 diabetes mellitus (T2DM), yet long-term use has been consistently associated with vitamin B12 deficiency. This study evaluates serum vitamin B12 levels in patients receiving metformin and examines dose-response and duration-response relationships.
Methods: A cross-sectional study was conducted among 51 adults with T2DM on metformin therapy and 51 age- and sex-matched non-diabetic controls. Demographic, clinical, and biochemical parameters were recorded. Serum vitamin B12 levels were compared between groups and analyzed across metformin dose, duration of therapy, and diabetes duration. Pearson correlation analysis assessed associations between vitamin B12 concentrations and clinical variables.
Results: Mean serum vitamin B12 levels were significantly lower in diabetics than controls (258.84 ± 107.30 pg/mL vs 415.02 ± 158.04 pg/mL, p<0.001). Vitamin B12 deficiency (<200 pg/mL) was observed in 35.3% of diabetics compared with 3.9% of controls. Longer metformin use and higher daily doses were strongly associated with lower vitamin B12 levels. Duration of metformin therapy (r = –0.58, p<0.001), daily metformin dose (r = –0.44, p=0.002), and duration of diabetes (r = –0.52, p<0.001) showed significant negative correlations with vitamin B12 concentration. Peripheral smear abnormalities—macrocytosis and hypersegmented neutrophils—were more frequent in the diabetic group.
Conclusions: Vitamin B12 levels are significantly reduced in patients receiving metformin, with a clear dose-dependent and duration-dependent decline. These findings reinforce the need for routine B12 monitoring in long-term metformin users.
