Implication of critical pharmacokinetic gene variants on therapeutic response to metformin in Type 2 diabetes

Pharmacogenomics. 2018 Jul 1;19(11):905-911. doi: 10.2217/pgs-2018-0041. Epub 2018 Jun 19.

Abstract

Aim: Metformin, an oral hypoglycemic drug is the first line of treatment for Type 2 diabetes individuals. We studied the effect of critical gene single nucleotide polymorphisms on the glucose lowering effect of metformin.

Method: We performed a prospective study on 221 newly diagnosed, treatment-naive Type 2 diabetes subjects. Individuals were started with metformin monotherapy and followed up for 12 weeks.

Results: Our association analysis revealed that SLC22A2 rs316019 and SLC47A2 rs12943590 were significantly associated with metformin drug response across co-dominant and dominant models, respectively. SLC22A2 rs316019 GG and SLC47A2 rs12943590 GA combined genotypes showed maximum average change in HbA1c level.

Conclusion: The present study proposes a role of SLC22A2 rs316019 and SLC47A2 rs12943590 in the pharmacokinetic action of metformin.

Keywords: Type 2 diabetes; metformin; multidrug and toxin extrusion; organic cation transporter; pharmacogenomics; pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genotype
  • Glycated Hemoglobin / genetics
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin / pharmacokinetics*
  • Metformin / therapeutic use*
  • Middle Aged
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transporter 2 / genetics
  • Pharmacogenomic Variants / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Prospective Studies

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 2
  • Metformin