Metformin With Either Histamine H2-Receptor Antagonists or Proton Pump Inhibitors: A Polypharmacy Recipe for Neuropathy via Vitamin B12 Depletion

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Metformin With Either Histamine H2-Receptor Antagonists or Proton Pump Inhibitors: A Polypharmacy Recipe for Neuropathy via Vitamin B₁₂ Depletion

Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV

Clinical Diabetes 2015 Apr; 33(2): 90-95. https://doi.org/10.2337/diaclin.33.2.90

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FIGURE 1.
Schematic representation of the sequelae of overweight/obesity and type 2 diabetes with regard to neuropathy and GERD. A positive feedback exists among neuropathy, GERD, management with acid-suppressing medications, and vitamin B₁₂ deficiency. The figure illustrates an additive effect of concomitant metformin and acid-suppression therapy leading to neuropathy via compounded vitamin B₁₂ depletion.

TABLE 1.

Incidence of Vitamin B₁₂ Deficiency Among Individuals Managed With Metformin

Study	Sample Size (n)	Individuals With B₁₂ Deficiency (n)	Individuals With B₁₂ Deficiency (%)
Tomkin et al., 1971 (28)	71	4^*	5.6
Adams et al., 1983 (29)	33	—^†	—
Hermann et al., 2004 (30)	53	19^‡	36
Pflipsen et al., 2009 (31)	195	44	23
Qureshi et al., 2001 (32)	70	23	33
Calvo Romero and Ramiro Lozano, 2012 (33)	81	7	8.6
Sato et al., 2013 (34)	62	8	13

↵* Twenty-one individuals (30%) were identified as having B₁₂ malabsorption.
↵† Twelve individuals (36%) were identified as having B₁₂ malabsorption.
↵‡ Individuals identified as being deficient had ≥1 abnormal B₁₂ marker (e.g., subnormal/reduced cobalamin, reduced holotranscobalamin, elevated homocysteine, and elevated methylmalonic acid)