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Polymorphism of Organic Cation Transporter 2 Improves Glucose-Lowering Effect of Metformin via Influencing Its Pharmacokinetics in Chinese Type 2 Diabetic Patients.
- Source :
- Molecular Diagnosis & Therapy; Feb2015, Vol. 19 Issue 1, p25-33, 9p
- Publication Year :
- 2015
-
Abstract
- Background and Objectives: This study aimed to investigate how the organic cation transporter 2 nucleotide polymorphism at site 808 (G → T) affects metformin pharmacokinetics and its long-term anti-diabetic effect. Methods: A total of 220 newly diagnosed type 2 diabetes patients taking oral metformin were recruited, genotyped and then divided into three groups by SLC22A2 genotypes (G/G, G/T, T/T). Nine patients in the GG genotype group, five patients in the GT genotype group and four patients in the TT genotype group were randomly selected for the metformin pharmacokinetic study. A randomized cohort study with 1-year follow-up was performed to clarify the metformin pharmacodynamics. Results: After 1 year, the decrease in glycosylated hemoglobin (HbA) levels in subjects with the heterozygous variant genotype (GT) was significantly greater than in those with the wild-type homozygote (−2.2 % in GT vs. −1.1 % in GG, P < 0.05) after adjustment for baseline HbA levels, exercise and diet in each group. There were also differences in the pharmacokinetic parameters (95 % confidence interval) of metformin between these two groups [area under the concentration-time curve (AUC) 19.7 (15.7-23.8) vs. 14.3 (11.7-16.9) μg h/L; renal clearance (CL) 16.8 (8.5-25.0) vs. 34.1 (24.9-43.2) L/h; tubular secretion clearance (CL) 8.1 (2.2-18.1) vs. 22.7 (15.5-29.8) L/h; all P < 0.05]. Multivariate analysis further revealed that the presence of T alleles and gender were independent influencing factors of urine excretion of metformin ( P < 0.05). Conclusion: As well as gender, the glucose-lowering efficiency of metformin can be enhanced by SLC22A2 808G > T variants through the delay of its transportation and CL in Chinese type 2 diabetes populations. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 11771062
- Volume :
- 19
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Molecular Diagnosis & Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 101047972
- Full Text :
- https://doi.org/10.1007/s40291-014-0126-z