Metformin and vitamin deficiency

Q: Metformin is known to cause the deficiency of which vitamin?

Answer:  Vitamin B12

Metformin and other biguanides reduce the absorption of vitamin B12, particularly in long-term patients. The effect is dose-dependent. The mechanism of action is via altered calcium homeostasis. Intestinal uptake of the vitamin B12-intrinsic factor complex requires calcium. The site of action is the ileum, where metfоrmin affects calcium-dependent membrane action. Fortunately, this action can be easily attenuated or reversed by calcium supplementation.

Diabetic patients are already prone to neuropathy, and in the long term, diabetic users of metformin without calcium supplementation may make it worse.

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References:

1. Ahmed MA, Muntingh G, Rheeder P. Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy. BMC Pharmacol Toxicol 2016; 17:44.

2. Mazokopakis EE, Starakis IK. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency. Diabetes Res Clin Pract 2012; 97:359.

3. Bauman WA, Shaw S, Jayatilleke E, et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000; 23:1227.