A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes

作者：Han Eugene; Park Hye Sun; Kwon Obin; Choe Eun Yeong; Wang Hye Jin; Lee Yong ho; Lee Sang Hak; Kim Chul Hoon; Kim Lee Kyung; Kwak Soo Heon; Park Kyong Soo; Kim Chul Sik^*; Kang Eun Seok^*

来源：Medicine, 2016, 95(44): e5155.

DOI：10.1097/MD.0000000000005155

• diabetes mellitus
• dipeptidyl peptidase-4 inhibitor
• glucagon-like peptide-1 receptor
• response
• type 2

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.

• 出版日期2016-11