SLC47A1 gene rs2289669 G&gt;A variants enhance the glucose-lowering effect of metformin via delaying its excretion in Chinese type 2 diabetes patients

He, Rui; Zhang, Dandan; Lü, Wei; Zheng, Tao; Wan, Lili; Liu, Fang; Wang, Jia

doi:10.1016/j.diabres.2015.05.003

Cited by 51 publications

(54 citation statements)

References 28 publications

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“…MATE1 plays an important role in metformin renal elimination, but the evidence suggesting a relationship between rs2289669 and the glucose response to metformin is controversial . The results of the present study were consistent with previous reports that showed that metformin had a better hypoglycaemic effect in people carrying the rs2289669 GA/AA genotypes .…”

Section: Discussionsupporting

confidence: 91%

Differential increments of basal glucagon‐like‐1 peptide concentration among SLC47A1 rs2289669 genotypes were associated with inter‐individual variability in glycaemic response to metformin in Chinese people with newly diagnosed Type 2 diabetes

Liang¹,

Xu²,

Zhou³

et al. 2017

Diabet. Med.

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show abstract

Section: Discussionsupporting

confidence: 91%

Differential increments of basal glucagon‐like‐1 peptide concentration among SLC47A1 rs2289669 genotypes were associated with inter‐individual variability in glycaemic response to metformin in Chinese people with newly diagnosed Type 2 diabetes

Liang¹,

Xu²,

Zhou³

et al. 2017

Diabet. Med.

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show abstract

“…The LSS model was further validated using data from 16 previously published studies . The results (Table , Figure , Supplementary Figures S7 and S8) indicated that the AUC(0,24 h) predicted by the two point LSS model was in excellent agreement ( r 2 = 0.976, bias −1.0%, precision 4.3%) with the corresponding AUC(0,24 h) best estimates, over a wide range (3.8–22.4 μg h l −1 ) of AUC(0,24 h) values and under a variety of demographic, experimental and clinical conditions.…”

Section: Resultsmentioning

confidence: 81%

Limited sampling strategy for determining metformin area under the plasma concentration–time curve

Santoro

Stage

Struchiner

et al. 2016

Brit J Clinical Pharma

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“…Recent studies suggested that metformin is also a substrate of renal MATE1 and MATE2‐K, which are expressed on the apical side of proximal tubular cells and have a similar substrate specificity as OCT2. Additionally, MATE1 polymorphism studies suggested that metformin plasma concentration and glucose‐lowering effect increased in the MATE1 variant (SLC47A1 rs2289669), which further confirmed that MATEs are involved in the renal secretion of metformin . Metformin and MATE1 interaction was further strengthened by the finding that pyrimethamine, a relatively selective and potent MATE1 inhibitor, can cause a 139% increase in metformin plasma AUC, which is attributed to the inhibition of renal clearance .…”

Section: Clinical Significance Of Renal Ddismentioning

confidence: 78%

Evaluation and Quantitative Prediction of Renal Transporter‐Mediated Drug‐Drug Interactions

Feng

Varma

2016

The Journal of Clinical Pharma

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With numerous drugs cleared renally, inhibition of uptake transporters localized on the basolateral membrane of renal proximal tubule cells, eg, organic anion transporters (OATs) and organic cation transporters (OCTs), may lead to clinically meaningful drug-drug interactions (DDIs). Additionally, clinical evidence for the possible involvement of efflux transporters, such as P-glycoprotein (P-gp) and multidrug and toxin extrusion protein 1/2-K (MATE1/2-K), in the renal DDIs is emerging. Herein, we review recent progress regarding mechanistic understanding of transporter-mediated renal DDIs as well as the quantitative predictability of renal DDIs using static and physiologically based pharmacokinetic (PBPK) models. Generally, clinical DDI data suggest that the magnitude of plasma exposure changes attributable to renal DDIs is less than 2-fold, unlike the DDIs associated with inhibition of cytochrome P-450s and/or hepatic uptake transporters. It is concluded that although there is a need for risk assessment early in drug development, current available data imply that safety concerns related to the renal DDIs are generally low. Nevertheless, consideration must be given to the therapeutic index of the victim drug and potential risk in a specific patient population (eg, renal impairment). Finally, in vitro transporter data and clinical pharmacokinetic parameters obtained from the first-in-human studies have proven useful in support of quantitative prediction of DDIs associated with inhibition of renal secretory transporters, OATs or OCTs.

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SLC47A1 gene rs2289669 G>A variants enhance the glucose-lowering effect of metformin via delaying its excretion in Chinese type 2 diabetes patients

Cited by 51 publications

References 28 publications

Differential increments of basal glucagon‐like‐1 peptide concentration among SLC47A1 rs2289669 genotypes were associated with inter‐individual variability in glycaemic response to metformin in Chinese people with newly diagnosed Type 2 diabetes

Differential increments of basal glucagon‐like‐1 peptide concentration among SLC47A1 rs2289669 genotypes were associated with inter‐individual variability in glycaemic response to metformin in Chinese people with newly diagnosed Type 2 diabetes

Limited sampling strategy for determining metformin area under the plasma concentration–time curve

Evaluation and Quantitative Prediction of Renal Transporter‐Mediated Drug‐Drug Interactions

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