<p>Diabetes mellitus (DM) is a global metabolic disorder characterised by chronic hyperglycemia resulting from insulin deficiency or resistance. Metformin, a first-line pharmacotherapy for type 2 diabetes mellitus (T2DM), effectively lowers blood glucose levels and improves insulin sensitivity. However, emerging evidence from studies indicates a significant association between long-term metformin use and vitamin B12 deficiency, with prevalence rates ranging from 6% to 66%. This study is a narrative literature review that summarises and interprets the available evidence on the association between metformin therapy and vitamin B12 deficiency in patients with type 2 diabetes mellitus. The mechanism primarily involves interference with calcium-dependent absorption of the vitamin B12–intrinsic factor complex in the ileum. Prolonged therapy and higher doses of metformin correlate with decreased serum B12 levels, contributing to neuropathy, anemia, and cognitive impairment in diabetic patients. Evidence from North America, Europe, Asia, Africa, and Latin America consistently highlights the need for routine B12 monitoring and supplementation, especially in elderly patients and those on high-dose or long-term therapy. Despite widespread recognition of this risk, clinical monitoring remains suboptimal. Proactive screening and targeted supplementation can prevent irreversible neurological and hematological complications, improving long-term outcomes in metformin-treated diabetic populations.</p> Graphical abstract <p></p>