Assessing Cognitive Responses and Serum Vitamin B₁₂ Levels in Newly Diagnosed Type 2 Diabetes Mellitus Patients Treated With Metformin: A Prospective Study.

Background Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment, and metformin, the first-line pharmacotherapy, has been linked to vitamin B₁₂ deficiency with potential neurological consequences. Objective evidence linking early metformin-induced changes in vitamin B₁₂ levels to cognitive function remains limited, particularly in Indian populations. Objectives To evaluate changes in serum vitamin B₁₂ status and cognitive function, assessed using P300 event-related potentials (ERPs), after six months of metformin therapy in newly diagnosed T2DM patients. Methods This prospective observational study included 52 adults (18-60 years) with newly diagnosed T2DM who were initiated on metformin monotherapy. Baseline and six-month assessments included serum vitamin B₁₂, homocysteine, methylmalonic acid (MMA), HbA1c, and cognitive evaluation using auditory oddball P300 ERPs. Changes over time were analyzed using the Wilcoxon signed-rank test, and correlations were assessed using Spearman's coefficient. Results After six months, blood sugar control improved significantly. The HbA1c level decreased from 7.8 (6.9-8.9) to 7.2 (6.5-8.1) (p = 0.001). However, serum vitamin B₁₂ levels decreased significantly, from 506.7 (347.3-613.5) to 485.0 (332.4-592.0) (p < 0.001). At the same time, homocysteine and MMA levels increased. Homocysteine increased from 16.5 (10.1-23.9) to 17.2 (10.8-25.0) μmol/L (p < 0.001), suggesting the development of functional vitamin B₁₂ deficiency. Additionally, P300 latency increased significantly at the frontal, central, and parietal electrode sites (p < 0.001), indicating slower cognitive processing. Although vitamin B₁₂ levels decreased, no statistically significant correlation was found between serum vitamin B₁₂ levels and P300 latency. Conclusion In newly diagnosed Indian patients with type 2 diabetes mellitus, six months of metformin therapy improved blood sugar control but was associated with early signs of functional vitamin B₁₂ deficiency and slower cognitive processing, as indicated by increased P300 latency. These results highlight the importance of regular monitoring of vitamin B₁₂ status, including functional markers like homocysteine and MMA. Early detection and correction of vitamin B₁₂ deficiency may help preserve cognitive function and support better long-term outcomes in patients on metformin therapy.