The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c

Pharmacogenetics and Genomics

Volumn 21, Issue 12, 2011, Pages 837-850

  Christensen, Mette M H ^a   Brasch Andersen, Charlotte ^b   Green, Henrik ^d,e   Nielsen, Flemming ^a   Damkier, Per ^b   Beck Nielsen, Henning ^c   Brosen, Kim ^a  

^a UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^b Department of Clinical Genetics ^*  (Denmark)

^c ODENSE UNIVERSITY HOSPITAL   (Denmark)

^d LINKÖPING UNIVERSITY   (Sweden)

^e SCIENCE FOR LIFE LABORATORY   (Sweden)

Author keywords

MATE1; MATE2; metformin; OCT1; OCT2; personalized medicine; pharmacogenetics; PMAT; steady state; type 2 diabetes

Indexed keywords

HEMOGLOBIN A1C; METFORMIN;

ADULT; ARTICLE; COHORT ANALYSIS; DOUBLE BLIND PROCEDURE; FEMALE; GENETIC VARIABILITY; GENOTYPE; GLYCOSYLATION; HUMAN; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; PHARMACOGENETICS; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; STEADY STATE;

EID: 81055140250     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e32834c0010     Document Type: Article

References (49)

1. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive bloodglucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352:854-865.
2. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355:2427-2443. (Pubitemid 44903747)
3. Bolen S, Feldman L, Vassy J, Wilson L, Yeh HC, Marinopoulos S, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 2007; 147:386-399. (Pubitemid 351664540)
4. Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 2005; 310:1642-1646. (Pubitemid 41780780)
5. Shu Y, Sheardown SA, Brown C, Owen RP, Zhang S, Castro RA, et al. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest 2007; 117:1422-1431. (Pubitemid 46718430)
6. Cusi K, Consoli A, DeFronzo RA. Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1996; 81:4059-4067. (Pubitemid 26380418)
7. Brunton LL. Goodman & Gilman's The pharmacological basis of therapeutics. 43: 11th edition New York: McGraw-Hill. 2005; pp. 1638-1639.
8. Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 2011; 50: 81-98.
9. Pentikainen PJ, Neuvonen PJ, Penttila A. Pharmacokinetics of metformin after intravenous and oral administration to man. Eur J Clin Pharmacol 1979; 16:195-202. (Pubitemid 10227380)
10. Xia L, Engel K, Zhou M,Wang J. Membrane localization and pH-dependent transport of a newly cloned organic cation transporter (PMAT) in kidney cells. Am J Physiol Renal Physiol 2007; 292:F682-F690. (Pubitemid 46220537)
11. Zhou M, Xia L, Engel K, Wang J. Molecular determinants of substrate selectivity of a novel organic cation transporter (PMAT) in the SLC29 family. J Biol Chem 2007; 282:3188-3195. (Pubitemid 47084340)
12. Zhou M, Xia L, Wang J. Metformin transport by a newly cloned protonstimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine. Drug Metab Dispos 2007; 35:1956-1962. (Pubitemid 47481592)
13. Koepsell H. Polyspecific organic cation transporters: their functions and interactions with drugs. Trends Pharmacol Sci 2004; 25: 375-381. (Pubitemid 38829491)
14. Koepsell H, Endou H. The SLC22 drug transporter family. Pflugers Arch 2004; 447:666-676. (Pubitemid 38241452)
15. Muller J, Lips KS, Metzner L, Neubert RH, Koepsell H, Brandsch M. Drug specificity and intestinal membrane localization of human organic cation transporters (OCT). Biochem Pharmacol 2005; 70:1851-1860. (Pubitemid 41612016)
16. Koepsell H, Lips K, Volk C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res 2007; 24:1227-1251. (Pubitemid 46876495)
17. Meyer Zu Schwabedissen HE, Verstuyft C, Kroemer HK, Becquemont L, Kim RB. Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2, and single nucleotide polymorphisms. Am J Physiol Renal Physiol 2010; 298:F997-F1005. Epub 2010. Jan 6. PubMed PMID: 20053795.
18. Leabman MK, Giacomini KM. Estimating the contribution of genes and environment to variation in renal drug clearance. Pharmacogenetics 2003; 13:581-584. (Pubitemid 37159636)
19. Shu Y, Brown C, Castro RA, Shi RJ, Lin ET, Owen RP, et al. Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clin Pharmacol Ther 2008; 83:273-280.
20. Tzvetkov MV, Vormfelde SV, Balen D, Meineke I, Schmidt T, Sehrt D, et al. The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clin Pharmacol Ther 2009; 86:299-306.
21. Becker ML, Visser LE, Van Schaik RH, Hofman A, Uitterlinden AG, Stricker BH. Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response. Pharmacogenet Genomics 2009; 20:38-44Pub. Med PMID: 19898263.
22. Becker ML, Visser LE, Van Schaik RH, Hofman A, Uitterlinden AG, Stricker BH. Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus. Pharmacogenomics J 2009; 9:242-247.
23. Becker ML, Visser LE, Van Schaik RH, Hofman A, Uitterlinden AG, Stricker BH. Genetic variation in the multidrug and toxin extrusion 1 transporter protein influences the glucose-lowering effect of metformin in patients with diabetes: a preliminary study. Diabetes 2009; 58:745-749.
24. Chen Y, Li S, Brown C, Cheatham S, Castro RA, Leabman MK, et al. Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin. Pharmacogenet Genomics 2009; 19: 497-504.
25. Song IS, Shin HJ, Shim EJ, Jung IS, Kim WY, Shon JH, et al. Genetic variants of the organic cation transporter 2 influence the disposition of metformin. Clin Pharmacol Ther 2008; 84:559-562.
26. Wang ZJ, Yin OQ, Tomlinson B, Chow MS. OCT2 polymorphisms and invivo renal functional consequence: studies with metformin and cimetidine. Pharmacogenet Genomics 2008; 18:637-645.
27. Choi JH,Wah YS, Kim MJ, Nguyen L, Lee SS, Kang JO, et al. Identification and characterization of novel polymorphisms in the basal promoter of the human transporter, MATE1. Pharmacogenet Genomics 2009; 19:770-780.
28. Kajiwara M, Terada T, Ogasawara K, Iwano J, Katsura T, Fukatsu A, et al. Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity. J Hum Genet 2009; 54: 40-46.
29. Gram J, Henriksen JE, Grodum E, Juhl H, Hansen TB, Christiansen C, et al. Pharmacological treatment of the pathogenetic defects in type 2 diabetes. The randomized multi-centre South Danish Diabetes study (SDDS). Diabetes Care 2010; 34:27-33Epub 2010 Oct 7. PubMed PMID: 20929990; Pub. Med Central PMCID: PMC3005476.
30. Ronaghi M, Uhlen M, Nyren P. A sequencing method based on real-time pyrophosphate. Science 1998; 281:363-365. (Pubitemid 28340773)
31. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16:31-41.
32. Nies AT, Koepsell H,Winter S, Burk O, Klein K, Kerb R, et al. Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology 2009; 50:1227-1240.
33. Cho SK, Yoon JS, Lee MG, Lee DH, Lim LA, Park K, et al. Rifampin enhances the glucose-lowering effect of metformin and increases OCT1 mRNA levels in healthy participants. Clin Pharmacol Ther 2011; 89:416-421.
34. Ahlin G, Chen L, Lazorova L, Chen Y, Ianculescu AG, Davis RL, et al. Genotype-dependent effects of inhibitors of the organic cation transporter, OCT1: predictions of metformin interactions. Pharmacogenomics J 2010 [Epub ahead of print] PubMed PMID: 20567254.
35. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21:263-265. (Pubitemid 40202029)
36. Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001; 68:978-989. (Pubitemid 32289743)
37. Stephens M, Scheet P. Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation. Am J Hum Genet 2005; 76:449-462. (Pubitemid 40250525)
38. Shu Y, Leabman MK, Feng B, Mangravite LM, Huang CC, Stryke D, et al. Evolutionary conservation predicts function of variants of the human organic cation transporter, OCT1. Proc Natl Acad Sci USA 2003; 100:5902-5907. (Pubitemid 36576905)
39. Kerb R, Brinkmann U, Chatskaia N, Gorbunov D, Gorboulev V, Mornhinweg E, et al. Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences. Pharmacogenetics 2002; 12:591-595. (Pubitemid 36005667)
40. Leabman MK, Huang CC, Kawamoto M, Johns SJ, Stryke D, Ferrin TE, et al. Polymorphisms in a human kidney xenobiotic transporter, OCT2, exhibit altered function. Pharmacogenetics 2002; 12:395-405. (Pubitemid 34816419)
41. Sambol NC, Chiang J, O'Conner M, Liu CY, Lin ET, Goodman AM, et al. Pharmacokinetics and pharmacodynamics of metformin in healthy subjects and patients with noninsulin-dependent diabetes mellitus. J Clin Pharmacol 1996; 36:1012-1021. (Pubitemid 27014728)
42. Sirtori CR, Franceschini G, Galli-Kienle M, Cighetti G, Galli G, Bondioli A, et al. Disposition of metformin (N,N-dimethylbiguanide) in man. Clin Pharmacol Ther 1978; 24:683-693. (Pubitemid 9120960)
43. Timmins P, Donahue S, Meeker J, Marathe P. Steady-state pharmacokinetics of a novel extended-release metformin formulation. Clin Pharmacokinet 2005; 44:721-729. (Pubitemid 40994081)
44. Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y. Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther 2002; 302:510-515. (Pubitemid 34787213)
45. Savic RM, Yee S, Giacomini KM KM. Effect of genetic variation in the organic cation transporter 1 and 2 on metformin pharmacokinetics: nonlinear mixed-effects analysis. Clin Pharmacol Ther 2011; 89 (supplement 1):5. Ref Type: Abstract.
46. http://www.ncbi.nlm.nih.gov/projects/SNP. 28-11-2009. Ref Type: Online Source.
47. Zhou K, Donnelly LA, Kimber CH, Donnan PT, Doney AS, Leese G, et al. Reduced-function SLC22A1 polymorphisms encoding organic cation transporter 1 and glycemic response to metformin: a GoDARTS study. Diabetes 2009; 58:1434-1439.
48. Zolk O. Current understanding of the pharmacogenomics of metformin. Clin Pharmacol Ther 2009; 86:595-598.
49. Zhou K, Bellenguez C, Spencer CC, Bennett AJ, Coleman RL, Tavendale R, et al. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet 2011; 43:117-120.