Metformin and megaloblastic anemia

Metformin is the most commonly prescribed oral medication for initial management and treatment of diabetes mellitus type 2. Common side effects of this drug include diarrhea, nausea/vomiting, and flatulence. However, a lesser known, more serious side effect is the development of megaloblastic anemia. According to Bell, D (2010) chronic metformin use can result in vitamin B12 deficiency in about 30% of patients.

Why is this significant?

Because in patients 65 and older, megaloblastic anemia caused by deficiencies of either cobalamin (vitamin B12) or folate (vitamin B9) is not uncommon. Therefore, the establishment of a hemoglobin/hematocrit baseline is useful before initiating metformin and for later reference. Additionally, the neurological findings associated with megaloblastic anemia from Vitamin B12 deficiency could be mistaken with diabetic peripheral neuropathy.


Diagnostic Testing useful in differentiating Vitamin B12 deficiency megaloblastic anemia from prolonged Metformin use megaloblastic anemia

• HgA1C (to rule out DM)
• CBC at baseline
• GFR at baseline
• Serum Folate
• Serum B12
• Homocysteine Level

References
Bell, D. (2010). Metformin-induced vitamin B12 deficiency presenting as a peripheral neuropathy. South Med J. 103(3):265-7. doi: 10.1097/SMJ.0b013e3181ce0e4d.

Epocrates. (2018). Metformin. Retrieved from https://online.epocrates.com/drugs/78705/metformin/Adverse-Reactions