Metformin-induced vitamin B12 deficiency: An underdiagnosed cause of diabetic neuropathy

Table 1 Clinical guideline recommendations on metformin-induced vitamin B12 deficiency

Guideline	Recommendation	Monitoring frequency	Treatment	Ref.
British Committee for Standards in Haematology	Does not recommend routine screening, but suggests evaluation if clinical suspicion exists; highlights the importance of ruling out pernicious anemia	Not specified	If due to metformin: Oral cobalamin 50 μg/day for 1 month; prophylactic supplementation not recommended	[46]
American Association of Clinical Endocrinologists and American College of Endocrinology-Clinical Practice Guidelines-2015	Mentions the risk of deficiency in metformin users	Not specified	No treatment specified	[40]
Diabetes Canada	Does not mention vitamin B12 deficiency	Not mentioned	Not mentioned	[42]
Diabetes Research and Clinical Practice-2023	Mentions vitamin B12 only as a differential diagnosis	Not mentioned	Not mentioned
Vitamin B12 deficiency in over 16 seconds: Diagnosis and management, guidance NICE	Recommend screening in patients with at least one symptom and one risk factor (such as metformin use)	Not specified	Oral or IM vitamin B12; reevaluate after 3 months; consider discontinuing metformin if it is the cause	[38]
ADA Standards of Care in Diabetes-2025	Acknowledges the risk of deficiency in patients with neuropathy or anemia, especially those taking > 1500 mg/day or using it for > 4-5 years	Periodic monitoring recommended, no specific interval defined	No specific treatment recommended	[39]

NICE: National Institute for Health and Care Excellence; ADA: American Diabetes Association; IM: Intramuscular.