title: A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes.
abstract: Incretin hormone-based therapy in type 2 diabetes has been widely used, and dipepdityl peptidase-4 (DPP-4) inhibitors, which prevent incretin degradation, have become popular oral hypoglycemic agents. The efficacy of DPP-4 inhibitors varies from individuals, and factors determining responses to DPP-4 inhibitors have not been fully established. We aimed to investigate whether genetic variations in glucagon-like peptide (GLP-1) receptor are associated with responses to DPP-4 inhibitors in patients with type 2 diabetes.Genetic variations of rs3765467 in GLP-1 receptor were explored in 246 patients with type 2 diabetes who received DPP-4 inhibitors treatment for 24 weeks in addition to previous medication. Patients with glycated hemoglobin (HbA1c) > 7% and who were naive to any DPP-4 inhibitors were enrolled. Responders were defined as those who showed a > 10% reduction in HbA1c after DPP-4 inhibitor treatment.DPP-4 inhibitors improved glycemic parameters and lipid profiles. Compared to the major genotype (GG), a larger proportion of patients with the minor allele genotype (GA/AA) were responders (P = 0.018), and also showing greater HbA1c reductions (1.3 ± 1.1 vs 0.9 ± 1.2%; P = 0.022). This genetic effect remained significant even after adjustment for other confounding factors (OR = 2.00, 95% CI = 1.03-3.89).Polymorphism in the GLP-1 receptor may influence DPP-4 inhibitor response. Further studies in larger population will help determine the association between genetic variation and interindividual differences in DPP-4 inhibitor therapy.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine Graduate school, Yonsei University College of Medicine Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan Brain Korea 21 Plus Project for Medical Science Division of Cardiology, Department of Internal Medicine Department of Pharmacology, Yonsei University College of Medicine Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Medical College, Gyeonggi-do, Korea.
authors.forename: Eugene
authors.initials: E
authors.lastname: Han
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Obin
authors.initials: O
authors.lastname: Kwon
authors.forename: Eun Yeong
authors.initials: EY
authors.lastname: Choe
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Wang
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Sang-Hak
authors.initials: SH
authors.lastname: Lee
authors.forename: Chul Hoon
authors.initials: CH
authors.lastname: Kim
authors.forename: Lee-Kyung
authors.initials: LK
authors.lastname: Kim
authors.forename: Soo Heon
authors.initials: SH
authors.lastname: Kwak
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Chul Sik
authors.initials: CS
authors.lastname: Kim
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D014644:Genetic Variation; D000067757:Glucagon-Like Peptide-1 Receptor / Q000235:genetics*; D006801:Humans; D054795:Incretins; D008297:Male; D008875:Middle Aged
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins