Table 1.

Possible role and effect of variations on metformin therapy

	SLC22A1	SLC22A2	SLC47A1	SLC47A2
Codes	OCT1	OCT2	MATE1	MATE2-K
Site	Hepatocytes, enterocytes	Renal distal tubule	Bile canalicular membrane of hepatocytes and in renal epithelium	Renal epithelium
Action	Mediates metformin uptake, accumulation and pharmacological action in the liver (AMPK activation)	Facilitates urinary elimination of metformin	Metformin secretion in bile and urine	Metformin excretion in urine
Variants	Decreased hepatic and intestinal metformin uptake and accumulation. Decreased AMPK activation. Increased plasma glucose levels and lower insulin levels	Decreased metformin clearance and increased plasma concentration	May affect glucose lowering effects of metformin. With each A allele there is an associated 0.3% HbA1C reduction. G allele has no association with HbA1C reduction