Genetic polymorphism of organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin: a narrative review

BackgroundOrganic cation transporter 2 (OCT2) is a renal carrier transporter protein found in the basolateral membrane of proximal epithelial cells, which facilitates active secretion of Metformin. The genetic polymorphism of OCT2 influences the pharmacodynamic and pharmacokinetic effect of Metformin in type 2 diabetes mellitus (T2DM) patients. This is also mainly associated with frequencies of the associated risk allele in a particular population.ObjectiveThe purpose of the study is to determine the impact of OCT2 genetic polymorphism on Metformin pharmacodynamics (PD) and pharmacokinetics (PK).Method of studyPreferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for performing the research. Following databases were used to conduct the search: PubMed/MEDLINE, Google Scholar, and the Cochrane Library. Relevant studies were retrieved and literatures were appraised for methodology, demographic characteristics, relevant SNPs, genetic intervention trials, and outcomes.ResultsBased on the data collected, 13 OCT2 Single nucleotide polymorphisms (SNPs) were identified across various ethnic groups. There were significant differences between the frequency distribution of shared alleles and impact of thirteen SNPs on Metformin. Among the thirteen OCT2 variants studied, rs316019 variant produced the most diverse responses in population by showing positive and negative impact on PK & PD of Metformin.Discussion and conclusionEach population's OCT2 polymorphism had a distinct effect on Metformin responsiveness. The findings of this study could bring significant benefits to patients with OCT2 genetic polymorphism if individualised T2DM therapy is introduced. Patient-centered treatment would improve the Metformin efficacy leading to new research in personalised medicine.