Context: Metformin is known to increase in the risk of developing vitamin B12 deficiency. This study aimed to compare the effectiveness of nasal spray of methylcobalamin (NASO B12) and methylcobalamin tablets for treating vitamin B12 deficiency in diabetic patients receiving metformin. Materials and Methods: In this parallel-group, comparative, open-label clinical study, patients (n = 100) were assigned to two groups: nasal spray of methylcobalamin (NASO B12) (methylcobalamin 250 µg/spray), sprayed in each nostril every alternate day for a total of seven doses (Group 1: a total of 3500 µg methylcobalamin per patient) and oral methylcobalamin tablets, a single daily dose of 1500 µg for a total of seven doses (Group 2: a total of 10,500 µg methylcobalamin per patient). The assessment of efficacy was carried out by measuring serum vitamin B12 levels at baseline, day 7, and day 14. Statistical Analysis Used: The analysis used is Student’s unpaired t-test. Results: NASO B12 treatment resulted in vitamin B12 levels of ≥400 pg/mL (recently updated normal levels as per American Academy of Family Physicians) in 86% and 92% of patients, on day 7 and day 14, respectively, whereas no patient attained ≥400 pg/mL with oral therapy. NASO B12 therapy resulted in higher mean vitamin B12 levels of 485.88 and 570.16 pg/mL when compared with 172.26 and 185.44 pg/mL with oral tablets on day 7 and day 14, respectively. Conclusion: NASO B12 provided much superior absorption of vitamin B12 when compared with oral vitamin B12 tablets and can be used as an effective alternative.