The pharmacogenetics of metformin

Diabetologia

Volumn 60, Issue 9, 2017, Pages 1648-1655

  Florez, Jose C ^a,b,c  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Genome wide association studies; Metformin; Pharmacogenetics; Review; Single nucleotide polymorphisms; Type 2 diabetes

Indexed keywords

METFORMIN;

AGNOSTIC; CLINICAL TRIAL (TOPIC); COHORT ANALYSIS; DRUG INDUSTRY; DRUG MECHANISM; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HUMAN; NON INSULIN DEPENDENT DIABETES MELLITUS; PHARMACOGENETICS; PRIORITY JOURNAL; REVIEW; TREATMENT RESPONSE; ANIMAL; GENETICS; PROCEDURES; SINGLE NUCLEOTIDE POLYMORPHISM;

ANIMALS; DIABETES MELLITUS, TYPE 2; GENOME-WIDE ASSOCIATION STUDY; HUMANS; METFORMIN; PHARMACOGENETICS; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 85026726925     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-017-4335-y     Document Type: Review

References (56)

1. Nathan DM, Buse JB, Davidson MB et al (2009) Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 52:17–30
2. Rodbard HW, Jellinger PS, Davidson JA et al (2009) Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract 15:540–559
3. Inzucchi SE, Bergenstal RM, Buse JB et al (2015) Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 58:429–442
4. Bailey CJ, Turner RC (1996) Metformin. N Engl J Med 334:574–579
5. Nathan DM (2007) Finding new treatments for diabetes—how many, how fast.. how good? N Engl J Med 356:437–440
6. The Diabetes Prevention Program Research Group (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403
7. Kirpichnikov D, McFarlane SI, Sowers JR (2002) Metformin: an update. Ann Intern Med 137:25–33
8. The United Kingdom Prospective Diabetes Study (1998) Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854–865
9. Knowler WC, Fowler SE, Hamman RF et al (2009) 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 374:1677–1686
10. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE (1995) Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med 333:550–554
11. The Diabetes Prevention Program Research Group (2012) Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 35:731–737
12. Aroda VR, Knowler WC, Crandall JP, Group DPPR (2017) Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study. Diabetologia doi:10.1007/s00125-017-4361-9
13. Sam S, Ehrmann DA (2017) Metformin therapy for the reproductive and metabolic consequences of polycystic ovary syndrome. Diabetologia doi:10.1007/s00125-017-4306-3
14. Heckman-Stoddard B (2017) Repurposing metformin for the prevention of cancer and cancer recurrence. Diabetologia doi:10.1007/s00125-017-4372-6
15. Turner RC, Cull CA, Frighi V, Holman RR (1999) Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 281:2005–2012
16. Kahn SE, Haffner SM, Heise MA et al (2006) Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2443
17. Zeitler P, Hirst K, Pyle L et al (2012) A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med 366:2247–2256
18. Rena G, Hardie DG, Pearson ER (2017) The mechanisms of action of metformin. Diabetologia doi:10.1007/s00125-017-4342-z
19. Williams LK, Padhukasahasram B, Ahmedani BK et al (2014) Differing effects of metformin on glycemic control by race-ethnicity. J Clin Endocrinol Metab 99:3160–3168
20. Lee SH, Wray NR, Goddard ME, Visscher PM (2011) Estimating missing heritability for disease from genome-wide association studies. Am J Hum Genet 88:294–305
21. GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group, Wellcome Trust Case Control Consortium, Zhou K et al (2011) Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet 43:117–120
22. Yang J, Lee SH, Goddard ME, Visscher PM (2011) GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet 88:76–82
23. Zhou K, Donnelly L, Yang J et al (2014) Heritability of variation in glycaemic response to metformin: a genome-wide complex trait analysis. Lancet Diabetes Endocrinol 2:481–487
24. Florez JC (2017) Pharmacogenetics in type 2 diabetes: precision medicine or discovery tool? Diabetologia 60:800–807
25. Graham GG, Punt J, Arora M et al (2011) Clinical pharmacokinetics of metformin. Clin Pharmacokinet 50:81–98
26. Zhou M, Xia L, Wang J (2007) Metformin transport by a newly cloned proton-stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine. Drug Metab Dispos 35:1956–1962
27. Muller J, Lips KS, Metzner L, Neubert RH, Koepsell H, Brandsch M (2005) Drug specificity and intestinal membrane localization of human organic cation transporters (OCT). Biochem Pharmacol 70:1851–1860
28. Chen L, Pawlikowski B, Schlessinger A et al (2010) Role of organic cation transporter 3 (SLC22A3) and its missense variants in the pharmacologic action of metformin. Pharmacogenet Genomics 20:687–699
29. Nies AT, Koepsell H, Winter S et al (2009) Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology 50:1227–1240
30. Shu Y, Sheardown SA, Brown C et al (2007) Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest 117:1422–1431
31. Otsuka M, Matsumoto T, Morimoto R, Arioka S, Omote H, Moriyama Y (2005) A human transporter protein that mediates the final excretion step for toxic organic cations. Proc Natl Acad Sci U S A 102:17923–17928
32. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K (2007) Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol 74:359–371
33. Takane H, Shikata E, Otsubo K, Higuchi S, Ieiri I (2008) Polymorphism in human organic cation transporters and metformin action. Pharmacogenomics 9:415–422
34. Masuda S, Terada T, Yonezawa A et al (2006) Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. J Am Soc Nephrol 17:2127–2135
35. Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE (2012) Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics 22:820–827
36. Kerb R, Brinkmann U, Chatskaia N et al (2002) Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences. Pharmacogenetics 12:591–595
37. Leabman MK, Huang CC, Kawamoto M et al (2002) Polymorphisms in a human kidney xenobiotic transporter, OCT2, exhibit altered function. Pharmacogenetics 12:395–405
38. Sakata T, Anzai N, Shin HJ et al (2004) Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions. Biochem Biophys Res Commun 313:789–793
39. Shu Y, Leabman MK, Feng B et al (2003) Evolutionary conservation predicts function of variants of the human organic cation transporter, OCT1. Proc Natl Acad Sci U S A 100:5902–5907
40. Shu Y, Brown C, Castro RA et al (2008) Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clin Pharmacol Ther 83:273–280
41. Zhou K, Donnelly LA, Kimber CH et al (2009) Reduced function SLC22A1 polymorphisms encoding organic cation transporter 1 (OCT1) and glycaemic response to metformin: a Go-DARTS study. Diabetes 58:1434–1439
42. Gram J, Henriksen JE, Grodum E et al (2011) Pharmacological treatment of the pathogenetic defects in type 2 diabetes: the randomized multicenter South Danish Diabetes Study. Diabetes Care 34:27–33
43. Christensen MM, Brasch-Andersen C, Green H et al (2011) The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c. Pharmacogenet Genomics 21:837–850
44. Sundelin EI, Gormsen LC, Jensen JB et al (2017) Genetic polymorphisms in organic cation transporter 1 attenuates hepatic metformin exposure in humans. Clin Pharmacol Ther doi:10.1002/cpt.701
45. Dujic T, Zhou K, Donnelly LA, Tavendale R, Palmer CN, Pearson ER (2015) Association of organic cation transporter 1 with intolerance to metformin in type 2 diabetes: a GoDARTS study. Diabetes 64:1786–1793
46. Becker ML, Visser LE, van Schaik RH, Hofman A, Uitterlinden AG, Stricker BH (2009) Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus. Pharm J 9:242–247
47. Tkáč I, Klimcakova L, Javorsky M et al (2013) Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes. Diabetes Obes Metab 15:189–191
48. Jablonski KA, McAteer JB, de Bakker PI et al (2010) Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. Diabetes 59:2672–2681
49. Shikata E, Yamamoto R, Takane H et al (2007) Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin. J Hum Genet 52:117–122
50. Dujic T, Zhou K, Yee SW et al (2017) Variants in pharmacokinetic transporters and glycaemic response to metformin: a MetGen meta-analysis. Clin Pharmacol Ther 101:763–772
51. van Leeuwen N, Nijpels G, Becker ML et al (2012) A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts. Diabetologia 55:1971–1977
52. Florez JC, Jablonski KA, Taylor A et al (2012) The C allele of ATM rs11212617 does not associate with metformin response in the diabetes prevention Program. Diabetes Care 35:1864–1867
53. Pawlyk AC, Giacomini KM, McKeon C, Shuldiner AR, Florez JC (2014) Metformin pharmacogenomics: current status and future directions. Diabetes 63:2590–2599
54. Zhou K, Yee SW, Seiser EL et al (2016) Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin. Nat Genet 48:1055–1059
55. Dupuis J, Langenberg C, Prokopenko I et al (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42:105–116
56. Rena G, Pearson ER, Sakamoto K (2012) Molecular action and pharmacogenetics of metformin: current understanding of an old drug. Diabetes Manag 2:439–452