How Metformin Causes Vitamin B12 deficiency?

Multiple studies have shown that metformin reduces serum B12 levels in 10–30% of patients. The effect increases with the duration of the therapy.

Decrease in vitamin B12 absorption and levels following metformin use typically starts as early as the 4th month.

Mechanisms of Vitamin B12 deficiency with Metformin Use:

It has been proposed that metformin reduces Vitamin B12 absorption by following mechanisms –

1. Alterations in small bowel motility which stimulates bacterial overgrowth and consequential vitamin B12 deficiency
2. Competitive inhibition or inactivation of vitamin B12 absorption
3. Alterations in intrinsic factor (IF) levels and interaction with the cubulin endocytic receptor
4. Inhibition of the calcium dependent absorption of the vitamin B12-IF complex at the terminal ileum

Reference:

Fatima, S., Noor, S. 2013. A review on effects of metformin on vitamin B12 status. American Journal of Phytomedicine and Clinical Therapeutics, 1(8):652-660.