Table 1 Organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin
S. no. | Population | Author | Study design | Total sample | Age (mean/range), years | Duration of treatment | Polymorphism | MAF | Pharmacokinetic outcome | Pharmacodynamic outcome | Substrate drug | Overall effect |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | Chinese population | Wang et al. [8] | Open-label | 112 | 21–32 | 2 weeks | rs316019 | 13.3 | Significant variation in Metformin CLr and CLt, AUC, t ½ based on genotype | NIL | Metformin—500 mg | Negative impact |
2 | Latvian population-T2DMpatients | Zaharenko et al. [13] | Prospective cohort | 131 | 22–37 | 3 years | rs7757336 | 0.132 | The plasma AUC ∞ of Metformin throughout the risk category was dramatically lower than those in the reference category (6.30 ± 1.51 g/mL) (P = 0.009) A significant difference was seen between the reference group and the risk group in Cmax in plasma | NIL | Metformin—500 mg | Negative impact |
3 | 94 Healthy—unrelated European Americans 66- unrelated African Americans population | Chen et al. [9] |  |  |  |  | rs316019 | 10 | People with heterozygous mutant allele (808G/T) or homozygous conventional allele (808G/G) had remarkably different Metformin clearance (CLR) (p < 0.005) as well as gross secretion (SrCLR) than those who were homozygous for either allele | NIL | 240 mL of water with 850 mg of metformin HCl tablet | Positive impact |
4 | Jordanian population-T2DMpatients | Al-Eitan et al. [14] |  | 212 | 56.64 ± 9.4 year |  | rs10755577 rs17588242 rs17589858 rs2928035 rs3127573 rs316024 rs316025 rs316026 rs533452 rs662301 | 0.18 0.25 0.25 0.19 0.08 0.21 0.24 0.42 0.29 0.05 |  | No significant association of glycemic control in T2DM patients taking Metformin was found | Metformin | No significant effect |
5 | Pakistani population-T2DMpatients | Moeez et al. [12] | Case–control study | 1200 | 35–80 years | 1 year | rs201919874 | 10.2 | The heterozygous genotype Ga was associated with Metformin response (p < 0.05) | NIL | Group A- 1500 mg Metformin q24hrs for six months Group B- 1000 mg Metformin + 80 mg Sulfonylurea for one or more year | Positive impact |
6 | Caucasian population-healthy volunteers | Christensen et al. [10] | Cohort study | 50 | 20–49 years |  | rs316019 | 13 | No impact on Metformin renal clearance (CLrenal) as well as secretory clearance was seen with the c.808 (G > T) mutation (CLsec). Participants having recessive alleles in c.808 had higher CLrenal and CLsec levels | NIL | Metformin—500 mg | Positive impact |
7 | Denmark population-healthy inhabitants | Kuhlmann et al. [11] | Open-label, nonrandomised study | 212 | 18–60 years |  | rs316019 |  | GFRi were strongly linked to Metformin CLrenal & AUC 0 to 24 h The CLrenal is unaffected by OCT2 genotypes | NIL | Metformin—500 mg | No impact |