SLCO1B1 polymorphism and oral antidiabetic drugs

Basic Clin Pharmacol Toxicol. 2010 Oct;107(4):775-81. doi: 10.1111/j.1742-7843.2010.00581.x.


Organic anion-transporting polypeptide 1B1 (OATP1B1; gene: SLCO1B1) is an influx transporter expressed on the sinusoidal membrane of human hepatocytes, where it mediates the uptake of its substrates from blood into liver. In vitro, the SLCO1B1 c.521T>C (p.Val174Ala) single-nucleotide polymorphism (SNP) has been associated with reduced and the c.388A>G (p.Asn130Asp) SNP with both enhanced and reduced transport activity of OATP1B1. In vivo in humans, the c.521C allele (present in SLCO1B1*5 and *15 haplotypes) is associated with decreased hepatic uptake and increased plasma concentrations of several OATP1B1 substrates. The SLCO1B1*1B (c.388G-c.521T) haplotype is associated with enhanced hepatic uptake and decreased plasma concentrations of some OATP1B1 substrates. The SLCO1B1 c.521CC genotype has been associated with an about 60-190% increased, and the SLCO1B1*1B/*1B genotype with an about 30% decreased area under the plasma concentration-time curve of repaglinide. Moreover, SLCO1B1 polymorphism can affect the extent of interaction between OATP1B1 inhibitors and repaglinide. Accordingly, SLCO1B1 genotyping may help in choosing the optimal starting dose of repaglinide. In Chinese individuals, the SLCO1B1 c.521C allele has been associated with increased plasma concentrations of nateglinide, but the association could not be replicated in Caucasians. SLCO1B1 genotype has had no effect on the pharmacokinetics of rosiglitazone, pioglitazone or their metabolites. The hepatic uptake of metformin is mediated by organic cation transporters 1 and 3, and the liver is not important for the elimination or action of the dipeptidylpeptidase 4 inhibitors sitagliptin, vildagliptin and saxagliptin. Therefore, SLCO1B1 polymorphism unlikely affects the response to these antidiabetics. Possible effects of SLCO1B1 polymorphism on sulfonylureas remain to be investigated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Alleles
  • Carbamates / pharmacokinetics
  • Cyclohexanes / pharmacokinetics
  • Genotype
  • Haplotypes
  • Humans
  • Hypoglycemic Agents / pharmacokinetics*
  • Liver-Specific Organic Anion Transporter 1
  • Nateglinide
  • Organic Anion Transporters / genetics*
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / pharmacokinetics
  • Pioglitazone
  • Piperidines / pharmacokinetics
  • Polymorphism, Genetic*
  • Rosiglitazone
  • Thiazolidinediones / pharmacokinetics


  • Carbamates
  • Cyclohexanes
  • Hypoglycemic Agents
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • Piperidines
  • SLCO1B1 protein, human
  • Thiazolidinediones
  • Rosiglitazone
  • Nateglinide
  • Phenylalanine
  • repaglinide
  • Pioglitazone