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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Pharmacogenetics of the Glucagon-like Peptide-1 Receptor Agonist Liraglutide: A Step Towards Personalized Type 2 Diabetes Management

Author(s): Artemis Kyriakidou, Theocharis Koufakis, Dimitrios G. Goulis, Yiannis Vasilopoulos, Pantelis Zebekakis and Kalliopi Kotsa*

Volume 27, Issue 8, 2021

Published on: 03 December, 2020

Page: [1025 - 1034] Pages: 10

DOI: 10.2174/1381612826666201203145654

Price: $65

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Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder with increasing prevalence and a significant burden of long-term complications. Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) are a novel treatment option for T2DM, exerting optimal effects on glucose control and weight loss, and pleiotropic actions. Pharmacogenetics, a promising research field of precision medicine, investigates how gene variations can affect individual response to drug therapy, assuming that the diverse genetic architecture of patients with T2DM could be partly associated with the considerable inter-individual variability in the therapeutic response to GLP-1 RAs. This review aims to summarize current evidence related to T2DM risk variants, affecting the incretin pathway, focus on the pharmacogenetics of the GLP-1 RA liraglutide, and discuss their potential clinical implications in the management of this complex disorder.

Methods: A literature search was performed using electronic biomedical databases, and the findings of key studies are summarized and discussed in this narrative review.

Results: Available evidence suggests the involvement of genetic polymorphisms in GLP-1 Rgene in variation in glycemic response, metabolic parameters and gastric emptying in people treated with liraglutide. Polymorphisms in CNR1, CTRB1/2, TMEM114 and CHST3 loci were also shown to be implicated in the disturbance of the incretin homeostasis in T2DM. These findings warrant further investigation by future studies.

Conclusion: Robust findings from pharmacogenetic studies might be used to identify good responders to liraglutide treatment, in terms of both glycemic and weight control, thus reinforcing the patient-centered approach of T2DM management.

Keywords: Type 2 diabetes mellitus, pharmacogenetics, incretins, glucagon-like peptide-1 receptor agonist, liraglutide, polymorphisms, genetic studies, personalized medicine.

[1]
American Diabetes Association 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes 2019. Diabetes Care 2019; 42(Suppl. 1): S13-28.
[PMID: 30559228]
[2]
Unnikrishnan R, Pradeepa R, Joshi SR, Mohan V. Type 2 diabetes: Demystifying the global epidemic. Diabetes 2017; 66: 1432-42.
[3]
Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 2003; 46: 3-19.
[http://dx.doi.org/10.1007/s00125-002-1009-0]
[4]
Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: Perspectives on the past, present, and future The Lancet 2014; 383: 1068-83.
[5]
Knop FK, Vilsbøll T, Højberg PV, et al. Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes 2007; 56(8): 1951-9.
[http://dx.doi.org/10.2337/db07-0100] [PMID: 17513701]
[6]
Vamanu E. Complementary Functional Strategy for Modulation of Human Gut Microbiota. Curr Pharm Des 2018; 24(35): 4144-9.
[http://dx.doi.org/10.2174/1381612824666181001154242] [PMID: 30277147]
[7]
Vilsbøll T, Holst JJ. Incretins, insulin secretion and Type 2 diabetes mellitus. Diabetologia 2004; 47(3): 357-66.
[http://dx.doi.org/10.1007/s00125-004-1342-6] [PMID: 14968296]
[8]
Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007; 87(4): 1409-39.
[http://dx.doi.org/10.1152/physrev.00034.2006] [PMID: 17928588]
[9]
Ugleholdt R, Zhu X, Deacon CF, Ørskov C, Steiner DF, Holst JJ. Impaired intestinal proglucagon processing in mice lacking prohormone convertase 1. Endocrinology 2004; 145(3): 1349-55.
[http://dx.doi.org/10.1210/en.2003-0801] [PMID: 14630721]
[10]
Larsen PJ, Tang-Christensen M, Holst JJ, Ørskov C. Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience 1997; 77(1): 257-70.
[http://dx.doi.org/10.1016/S0306-4522(96)00434-4] [PMID: 9044391]
[11]
Meier JJ, Nauck MA. Glucagon-like peptide 1(GLP-1) in biology and pathology. Diabetes Metab Res Rev 2005; 21(2): 91-117.
[http://dx.doi.org/10.1002/dmrr.538] [PMID: 15759282]
[12]
Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007; 132(6): 2131-57.
[http://dx.doi.org/10.1053/j.gastro.2007.03.054] [PMID: 17498508]
[13]
Li W-Z, Stirling K, Yang J-J, Zhang L. Gut microbiota and diabetes: From correlation to causality and mechanism. World J Diabetes 2020; 11(7): 293-308.
[http://dx.doi.org/10.4239/wjd.v11.i7.293] [PMID: 32843932]
[14]
Kyriachenko Y, Falalyeyeva T, Korotkyi O, Molochek N, Kobyliak N. Crosstalk between gut microbiota and antidiabetic drug action. World J Diabetes 2019; 10(3): 154-68.
[http://dx.doi.org/10.4239/wjd.v10.i3.154] [PMID: 30891151]
[15]
Egan JM, Bulotta A, Hui H, Perfetti R. GLP-1 receptor agonists are growth and differentiation factors for pancreatic islet beta cells. Diabetes Metab Res Rev 2003; 19(2): 115-23.
[http://dx.doi.org/10.1002/dmrr.357] [PMID: 12673779]
[16]
Davies MJ, D’Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the european association for the study of diabetes (EASD). Diabetes Care 2018; 41: 2669-701.
[17]
Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2019; 2019(Aug): 31.
[PMID: 31497854]
[18]
Esposito K, Mosca C, Brancario C, Chiodini P, Ceriello A, Giugliano D. GLP-1 receptor agonists and HBA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials. Curr Med Res Opin 2011; 27(8): 1519-28.
[http://dx.doi.org/10.1185/03007995.2011.590127] [PMID: 21663496]
[19]
Inzucchi S. Management of Hyperglycemia in Type 2 Diabetes A Patient-Centered Approach. Diabetes Spectr 2012; 25(3): 154-71.
[20]
Vilsbøll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 2012; 344(7841): d7771.
[http://dx.doi.org/10.1136/bmj.d7771] [PMID: 22236411]
[22]
Scott SA. Personalizing medicine with clinical pharmacogenetics. Genet Med 2011; 13(12): 987-95.
[http://dx.doi.org/10.1097/GIM.0b013e318238b38c] [PMID: 22095251]
[23]
Carrasco-Ramiro F, Peiró-Pastor R, Aguado B. Human genomics projects and precision medicine. Gene Ther 2017; 24: 551-61.
[24]
Lindpaintner K. Pharmacogenetics and the future of medical practice. British Journal of Clinical Pharmacology 2002; 221-30.
[http://dx.doi.org/10.1046/j.1365-2125.2002.01630.x]
[25]
Morris AP, Voight BF, Teslovich TM, et al. Wellcome Trust Case Control Consortium; Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators; Genetic Investigation of ANthropometric Traits (GIANT) Consortium; Asian Genetic Epidemiology Network-Type 2 Diabetes (AGEN-T2D) Consortium; South Asian Type 2 Diabetes (SAT2D) Consortium; DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 2012; 44(9): 981-90.
[http://dx.doi.org/10.1038/ng.2383] [PMID: 22885922]
[26]
Fuchsberger C, Flannick J, Teslovich TM, et al. The genetic architecture of type 2 diabetes. Nature 2016; 536(7614): 41-7.
[http://dx.doi.org/10.1038/nature18642] [PMID: 27398621]
[27]
Tkáč I, Gotthardová I. Pharmacogenetic aspects of the treatment of Type 2 diabetes with the incretin effect enhancers. Pharmacogenomics 2016; 17: 795-804.
[28]
Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol 2012; 8(12): 728-42.
[http://dx.doi.org/10.1038/nrendo.2012.140] [PMID: 22945360]
[29]
Knudsen LB, Nielsen PF, Huusfeldt PO, et al. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem 2000; 43(9): 1664-9.
[http://dx.doi.org/10.1021/jm9909645] [PMID: 10794683]
[30]
Ostawal A, Mocevic E, Kragh N, Xu W. Clinical Effectiveness of Liraglutide in Type 2 Diabetes Treatment in the Real-World Setting: A Systematic Literature Review. Diabetes Ther 2016; 7(3): 411-38.
[http://dx.doi.org/10.1007/s13300-016-0180-0] [PMID: 27350545]
[31]
Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab 2017; 19(4): 524-36.
[http://dx.doi.org/10.1111/dom.12849] [PMID: 27981757]
[32]
Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006; 368(9548): 1696-705.
[http://dx.doi.org/10.1016/S0140-6736(06)69705-5] [PMID: 17098089]
[33]
Zhao L, Chen Y, Xia F, et al. A glucagon-like peptide-1 receptor agonist lowers weight by modulating the structure of gut microbiota. Front Endocrinol (Lausanne) 2018; 9: 233.
[http://dx.doi.org/10.3389/fendo.2018.00233] [PMID: 29867765]
[34]
Marso SP, Daniels GH, Brown-Frandsen K, et al. LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375(4): 311-22.
[http://dx.doi.org/10.1056/NEJMoa1603827] [PMID: 27295427]
[35]
Visscher PM, Brown MA, McCarthy MI, Yang J. Five years of GWAS discovery. Am J Hum Genet 2012; 90(1): 7-24.
[http://dx.doi.org/10.1016/j.ajhg.2011.11.029] [PMID: 22243964]
[36]
Guo X, Rotter JI. Genome-Wide Association Studies. JAMA 2019; 322: 1705-6.
[http://dx.doi.org/10.1001/jama.2019.16479]
[37]
McCarthy S, Das S, Kretzschmar W, et al. Haplotype Reference Consortium. A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet 2016; 48(10): 1279-83.
[http://dx.doi.org/10.1038/ng.3643] [PMID: 27548312]
[38]
Bush WS, Moore JH. Chapter 11: Genome-wide association studies. PLOS Comput Biol 2012; 8(12)
[http://dx.doi.org/10.1371/journal.pcbi.1002822] [PMID: 23300413]
[39]
Prasad RB, Groop L. Genetics of type 2 diabetes-pitfalls and possibilities. Genes (Basel) 2015; 6(1): 87-123.
[http://dx.doi.org/10.3390/genes6010087] [PMID: 25774817]
[40]
Müssig K, Staiger H, Machicao F, Häring HU, Fritsche A. Genetic variants affecting incretin sensitivity and incretin secretion. Diabetologia 2010; 53(11): 2289-97.
[http://dx.doi.org/10.1007/s00125-010-1876-8] [PMID: 20714888]
[41]
Babenko AP, Polak M, Cavé H, et al. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med 2006; 355(5): 456-66.
[http://dx.doi.org/10.1056/NEJMoa055068] [PMID: 16885549]
[42]
Pearson ER, Flechtner I, Njølstad PR, et al. l. Neonatal Diabetes International Collaborative Group. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med 2006; 355(5): 467-77.
[http://dx.doi.org/10.1056/NEJMoa061759] [PMID: 16885550]
[43]
Misra S, Owen KR. Genetics of Monogenic Diabetes: Present Clinical Challenges. Vol. 18, Current Diabetes Reports. Current Medicine Group 2018; LLC: 1.
[44]
Pearson ER, Starkey BJ, Powell RJ, Gribble FM, Clark PM, Hattersley AT. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet 2003; 362(9392): 1275-81.
[http://dx.doi.org/10.1016/S0140-6736(03)14571-0] [PMID: 14575972]
[45]
Maruthur NM, Gribble MO, Bennett WL, et al. The pharmacogenetics of type 2 diabetes: a systematic review. Diabetes Care 2014; 37(3): 876-86.
[http://dx.doi.org/10.2337/dc13-1276] [PMID: 24558078]
[46]
Mannino GC, Andreozzi F, Sesti G. Pharmacogenetics of type 2 diabetes mellitus, the route toward tailored medicine. Diabetes Metab Res Rev 2019; 35(3)
[http://dx.doi.org/10.1002/dmrr.3109] [PMID: 30515958]
[47]
Song J, Yang Y, Mauvais-Jarvis F, Wang YP, Niu T. KCNJ11, ABCC8 and TCF7L2 polymorphisms and the response to sulfonylurea treatment in patients with type 2 diabetes: a bioinformatics assessment. BMC Med Genet 2017; 18(1): 64.
[http://dx.doi.org/10.1186/s12881-017-0422-7] [PMID: 28587604]
[48]
Zhou K, Bellenguez C, Spencer CCA, et al. GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group; Wellcome Trust Case Control Consortium 2; MAGIC investigators. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet 2011; 43(2): 117-20.
[http://dx.doi.org/10.1038/ng.735] [PMID: 21186350]
[49]
Tokuyama Y, Matsui K, Egashira T, Nozaki O, Ishizuka T, Kanatsuka A. Five missense mutations in glucagon-like peptide 1 receptor gene in Japanese population. Diabetes Res Clin Pract 2004; 66(1): 63-9.
[http://dx.doi.org/10.1016/j.diabres.2004.02.004] [PMID: 15364163]
[50]
Beinborn M, Worrall CI, McBride EW, Kopin AS. A human glucagon-like peptide-1 receptor polymorphism results in reduced agonist responsiveness. Regul Pept 2005; 130(1-2): 1-6.
[http://dx.doi.org/10.1016/j.regpep.2005.05.001] [PMID: 15975668]
[51]
Sathananthan A, Man CD, Micheletto F, et al. Common genetic variation in GLP1R and insulin secretion in response to exogenous GLP-1 in nondiabetic subjects: a pilot study. Diabetes Care 2010; 33(9): 2074-6.
[http://dx.doi.org/10.2337/dc10-0200] [PMID: 20805279]
[52]
Koole C, Wootten D, Simms J, et al. Polymorphism and ligand dependent changes in human glucagon-like peptide-1 receptor (GLP-1R) function: allosteric rescue of loss of function mutation. Mol Pharmacol 2011; 80(3): 486-97.
[http://dx.doi.org/10.1124/mol.111.072884] [PMID: 21616920]
[53]
Lin CH, Lee YS, Huang YY, Hsieh SH, Chen ZS, Tsai CN. Polymorphisms of GLP-1 receptor gene and response to GLP-1 analogue in patients with poorly controlled type 2 diabetes. J Diabetes Res 2015.
[54]
Mahajan A, Go MJ, Zhang W, et al. Diabetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium; Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium; South Asian Type 2 Diabetes (SAT2D) Consortium; Mexican American Type 2 Diabetes (MAT2D) Consortium; Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat Genet 2014; 46(3): 234-44.
[http://dx.doi.org/10.1038/ng.2897] [PMID: 24509480]
[55]
Wessel J, Chu AY, Willems SM, et al. EPIC-InterAct Consortium. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. Nat Commun 2015; 6: 5897.
[http://dx.doi.org/10.1038/ncomms6897] [PMID: 25631608]
[56]
Tong Y, Lin Y, Zhang Y, et al. Association between TCF7L2 gene polymorphisms and susceptibility to type 2 diabetes mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis. BMC Med Genet 2009; 10: 15.
[http://dx.doi.org/10.1186/1471-2350-10-15] [PMID: 19228405]
[57]
da Silva Xavier G, Loder MK, McDonald A, et al. TCF7L2 regulates late events in insulin secretion from pancreatic islet β-cells. Diabetes 2009; 58(4): 894-905.
[http://dx.doi.org/10.2337/db08-1187] [PMID: 19168596]
[58]
Shu L, Matveyenko AV, Kerr-Conte J, Cho JH, McIntosh CHS, Maedler K. Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Hum Mol Genet 2009; 18(13): 2388-99.
[http://dx.doi.org/10.1093/hmg/ddp178] [PMID: 19386626]
[59]
Shao W, Wang D, Chiang YT, et al. The Wnt signaling pathway effector TCF7L2 controls gut and brain proglucagon gene expression and glucose homeostasis. Diabetes 2013; 62(3): 789-800.
[http://dx.doi.org/10.2337/db12-0365] [PMID: 22966074]
[60]
Schäfer SA, Tschritter O, Machicao F, et al. Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia 2007; 50(12): 2443-50.
[http://dx.doi.org/10.1007/s00125-007-0753-6] [PMID: 17661009]
[61]
Pilgaard K, Jensen CB, Schou JH, et al. The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. Diabetol 2009; 52(7): 1298-307.
[http://dx.doi.org/10.1007/s00125-009-1307-x] [PMID: 19288077]
[62]
Smushkin G, Sathananthan M, Sathananthan A, et al. Diabetes-associated common genetic variation and its association with GLP-1 concentrations and response to exogenous GLP-1. Diabetes 2012; 61(5): 1082-9.
[http://dx.doi.org/10.2337/db11-1732] [PMID: 22461567]
[63]
Ferreira MC, da Silva MER, Fukui RT, do Carmo Arruda-Marques M, Azhar S, Dos Santos RF. Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes. Diabetol Metab Syndr 2019; 11(1): 10.
[http://dx.doi.org/10.1186/s13098-019-0401-6] [PMID: 30700996]
[64]
Sandhu MS, Weedon MN, Fawcett KA, et al. Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet 2007; 39(8): 951-3.
[http://dx.doi.org/10.1038/ng2067] [PMID: 17603484]
[65]
Urano F. Wolfram Syndrome: Diagnosis, Management, and Treatment. Vol. 16, Current Diabetes Reports. Current Medicine Group LLC 2016; 1: 1-8.
[66]
Schäfer SA, Müssig K, Staiger H, et al. A common genetic variant in WFS1 determines impaired glucagon-like peptide-1-induced insulin secretion. Diabetologia 2009; 52(6): 1075-82.
[http://dx.doi.org/10.1007/s00125-009-1344-5] [PMID: 19330314]
[67]
Simonis-Bik AM, Nijpels G, van Haeften TW, et al. Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic β-cell function. Diabetes 2010; 59(1): 293-301.
[http://dx.doi.org/10.2337/db09-1048] [PMID: 19833888]
[68]
Pereira MJ, Lundkvist P, Kamble PG, et al. A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus Placebo in Individuals with Obesity and Without Diabetes: Metabolic Effects and Markers Associated with Bodyweight Loss. Diabetes Ther 2018; 9(4): 1511-32.
[http://dx.doi.org/10.1007/s13300-018-0449-6] [PMID: 29949016]
[69]
Unoki H, Takahashi A, Kawaguchi T, et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet 2008; 40(9): 1098-102.
[http://dx.doi.org/10.1038/ng.208] [PMID: 18711366]
[70]
Yasuda K, Miyake K, Horikawa Y, et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet 2008; 40(9): 1092-7.
[http://dx.doi.org/10.1038/ng.207] [PMID: 18711367]
[71]
Vallon V, Grahammer F, Volkl H, et al. KCNQ1-dependent transport in renal and gastrointestinal epithelia. Proc Natl Acad Sci USA 2005; 102(49): 17864-9.
[http://dx.doi.org/10.1073/pnas.0505860102] [PMID: 16314573]
[72]
Thévenod F. Ion channels in secretory granules of the pancreas and their role in exocytosis and release of secretory proteins. Am J Physiol Cell Physiol 2002; 283(3): C651-72.
[http://dx.doi.org/10.1152/ajpcell.00600.2001] [PMID: 12176723]
[73]
Müssig K, Staiger H, Machicao F, et al. Association of type 2 diabetes candidate polymorphisms in KCNQ1 with incretin and insulin secretion. Diabetes 2009; 58(7): 1715-20.
[http://dx.doi.org/10.2337/db08-1589] [PMID: 19366866]
[74]
Zeggini E, Scott LJ, Saxena R, et al. Wellcome Trust Case Control Consortium. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 2008; 40(5): 638-45.
[http://dx.doi.org/10.1038/ng.120] [PMID: 18372903]
[75]
Tuomi T, Nagorny CLF, Singh P, et al. Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. Cell Metab 2016; 23(6): 1067-77.
[http://dx.doi.org/10.1016/j.cmet.2016.04.009] [PMID: 27185156]
[76]
Clee SM, Yandell BS, Schueler KM, et al. Positional cloning of Sorcs1, a type 2 diabetes quantitative trait locus. Nat Genet 2006; 38(6): 688-93.
[http://dx.doi.org/10.1038/ng1796] [PMID: 16682971]
[77]
Goodarzi MO, Lehman DM, Taylor KD, et al. SORCS1: a novel human type 2 diabetes susceptibility gene suggested by the mouse. Diabetes 2007; 56(7): 1922-9.
[http://dx.doi.org/10.2337/db06-1677] [PMID: 17426289]
[78]
Zhou LM, Xu W, Yan XM, Li MXY, Liang H, Weng JP. Association between SORCS1 rs1416406 and therapeutic effect of exenatide 2017; 97(18): 1415-9.
[PMID: 28535629]
[79]
de Luis DA, Diaz Soto G, Izaola O, Romero E. Evaluation of weight loss and metabolic changes in diabetic patients treated with liraglutide, effect of RS 6923761 gene variant of glucagon-like peptide 1 receptor. J Diabetes Complications 2015; 29(4): 595-8.
[http://dx.doi.org/10.1016/j.jdiacomp.2015.02.010] [PMID: 25825013]
[80]
de Luis DA, Aller R, Izaola O, et al. Evaluation of weight loss and adipocytokine levels after two hypocaloric diets with different macronutrient distribution in obese subjects with the rs6923761 gene variant of glucagon-like peptide 1 receptor. Ann Nutr Metab 2013; 63(4): 277-82.
[http://dx.doi.org/10.1159/000356710] [PMID: 24334921]
[81]
de Luis DA, Aller R, de la Fuente B, et al. Relation of the rs6923761 gene variant in glucagon-like peptide 1 receptor with weight, cardiovascular risk factor, and serum adipokine levels in obese female subjects. J Clin Lab Anal 2015; 29(2): 100-5.
[http://dx.doi.org/10.1002/jcla.21735] [PMID: 24687535]
[82]
de Luis DA, Pacheco D, Aller R, Izaola O, Bachiller R. Roles of rs 6923761 gene variant in glucagon-like peptide 1 receptor on weight, cardiovascular risk factor and serum adipokine levels in morbid obese patients. Nutr Hosp 2014; 29(4): 889-93.
[PMID: 24679032]
[83]
Jensterle M, Pirš B, Goričar K, Dolžan V, Janež A. Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study. Eur J Clin Pharmacol 2015; 71(7): 817-24.
[http://dx.doi.org/10.1007/s00228-015-1868-1] [PMID: 25991051]
[84]
Imai K, Tsujimoto T, Goto A, et al. Prediction of response to GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes. Diabetol Metab Syndr 2014; 6(1): 110.
[http://dx.doi.org/10.1186/1758-5996-6-110] [PMID: 25349635]
[85]
Lean MEJ, Carraro R, Finer N, et al. NN8022-1807 Investigators. Tolerability of nausea and vomiting and associations with weight loss in a randomized trial of liraglutide in obese, non-diabetic adults. Int J Obes 2014; 38(5): 689-97.
[http://dx.doi.org/10.1038/ijo.2013.149] [PMID: 23942319]
[86]
Niswender K, Pi-Sunyer X, Buse J, et al. Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme. Diabetes Obes Metab 2013; 15(1): 42-54.
[http://dx.doi.org/10.1111/j.1463-1326.2012.01673.x] [PMID: 22862847]
[87]
Näslund E, Grybäck P, Backman L, et al. Distal small bowel hormones: correlation with fasting antroduodenal motility and gastric emptying. Dig Dis Sci 1998; 43(5): 945-52.
[http://dx.doi.org/10.1023/A:1018806129102] [PMID: 9590405]
[88]
Acosta A, Camilleri M, Shin A, et al. Quantitative gastrointestinal and psychological traits associated with obesity and response to weight-loss therapy. Gastroenterology 2015; 148(3): 537-546.e4.
[http://dx.doi.org/10.1053/j.gastro.2014.11.020] [PMID: 25486131]
[89]
Chedid V, Vijayvargiya P, Carlson P, et al. Allelic variant in the glucagon-like peptide 1 receptor gene associated with greater effect of liraglutide and exenatide on gastric emptying: A pilot pharmacogenetics study. Neurogastroenterol Motil 2018; 30(7)
[http://dx.doi.org/10.1111/nmo.13313] [PMID: 29488276]
[90]
Felder CC, Glass M. Cannabinoid receptors and their endogenous agonists. Annu Rev Pharmacol Toxicol 1998; 38: 179-200.
[http://dx.doi.org/10.1146/annurev.pharmtox.38.1.179] [PMID: 9597153]
[91]
Ameri A. The effects of cannabinoids on the brain. Prog Neurobiol 1999; 58(4): 315-48.
[http://dx.doi.org/10.1016/S0301-0082(98)00087-2] [PMID: 10368032]
[92]
Antonio de Luis D, Sagrado MG, Aller R, et al. Role of G1359A polymorphism of the cannabinoid receptor gene on weight loss and adipocytokines levels after two different hypocaloric diets. J Nutr Biochem 2012; 23(3): 287-91.
[http://dx.doi.org/10.1016/j.jnutbio.2010.12.006] [PMID: 21543209]
[93]
De Luis DA, González Sagrado M, Aller R, et al. Roles of G1359A polymorphism of the cannabinoid receptor gene (CNR1) on weight loss and adipocytokines after a hypocaloric diet. Nutr Hosp 2011; 26(2): 317-22.
[PMID: 21666969]
[94]
Aberle J, Fedderwitz I, Klages N, George E, Beil FU. Genetic variation in two proteins of the endocannabinoid system and their influence on body mass index and metabolism under low fat diet. Horm Metab Res 2007; 39(5): 395-7.
[http://dx.doi.org/10.1055/s-2007-977694] [PMID: 17533584]
[95]
Gadzicki D, Müller-Vahl K, Stuhrmann M. A frequent polymorphism in the coding exon of the human cannabinoid receptor (CNR1) gene. Mol Cell Probes 1999; 13(4): 321-3.
[http://dx.doi.org/10.1006/mcpr.1999.0249] [PMID: 10441206]
[96]
de Luis DA, Ovalle HF, Soto GD, Izaola O, de la Fuente B, Romero E. Role of genetic variation in the cannabinoid receptor gene (CNR1) (G1359A polymorphism) on weight loss and cardiovascular risk factors after liraglutide treatment in obese patients with diabetes mellitus type 2. J Investig Med 2014; 62(2): 324-7.
[http://dx.doi.org/10.2310/JIM.0000000000000032] [PMID: 24322329]
[97]
Voight BF, Kang HM, Ding J, Palmer CD, Sidore C, Chines PS, et al. The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic. Cardiovascular, and Anthropometric Traits PLoS Genet 2012; 8(8)e1002793
[98]
T Hart LM, Fritsche A, Nijpels G, Van Leeuwen N, Donnelly LA, Dekker JM, et al. The CTRB1/2 locus affects diabetes susceptibility and treatment via the incretin pathway. Diabetes 2013; 62(9): 3275-81.
[99]
T Hart LM, Simonis-Bik AM, Nijpels G, Van Haeften TW, Schäfer SA, Houwing-Duistermaat JJ, et al. . Combined risk allele score of eight type 2 diabetes genes is associated with reduced first-phase glucose-stimulated insulin secretion during hyperglycemic clamps. Diabetes 2010; 59(1): 287-92.
[100]
Fritsche A, Madaus A, Renn W, et al. The prevalent Gly1057Asp polymorphism in the insulin receptor substrate-2 gene is not associated with impaired insulin secretion. J Clin Endocrinol Metab 2001; 86(10): 4822-5.
[http://dx.doi.org/10.1210/jcem.86.10.7930] [PMID: 11600548]
[101]
Barrett JC, Clayton DG, Concannon P, et al. Type 1 Diabetes Genetics Consortium. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 2009; 41(6): 703-7.
[http://dx.doi.org/10.1038/ng.381] [PMID: 19430480]
[102]
Pearson ER. Diabetes: Is There a Future for Pharmacogenomics Guided Treatment? Clin Pharmacol Ther 2019; 106(2): 329-37.
[http://dx.doi.org/10.1002/cpt.1484] [PMID: 31012484]
[103]
Kalra S, Das AK, Bajaj S, Priya G, Ghosh S, Mehrotra RN, et al. Utility of Precision Medicine in the Management of Diabetes: Expert Opinion from an International Panel. Diabetes Therapy Adis 2020; 11: 411-22.
[104]
Heo CU, Choi C-I. Current Progress in Pharmacogenetics of Second-Line Antidiabetic Medications: Towards Precision Medicine for Type 2 Diabetes. J Clin Med 2019; 8(3): 393.
[http://dx.doi.org/10.3390/jcm8030393] [PMID: 30901912]
[105]
Karras SN, Rapti E, Koufakis T, Kyriazou A, Goulis DG, Kotsa K. Pharmacogenetics of Glucagon-like Peptide-1 Agonists for the Treatment of Type 2 Diabetes Mellitus. Curr Clin Pharmacol 2017; 12(4): 202-9.
[http://dx.doi.org/10.2174/1574884713666180221121512] [PMID: 29473524]

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