Aim: We examined associations of eight SNPs in/near seven candidate genes with glycemic response to 6 month treatment with DPP4 inhibitors. Patients & methods: 206 patients with type 2 diabetes (116 men and 90 women) were treated with sitagliptin or vildagliptin (both 100 mg/day) in combination with metformin or metformin/sulphonylurea over 6 months, and the reduction in glycated hemoglobin (HbA1c) was measured. Results: Rs6923761 in GLP1R was significantly associated with a reduction in HbA1c (adjusted p = 0.006). Homozygotes for the minor A allele had smaller reduction in HbA1c by 0.4% (4 mmol/mol) than the G allele carriers (p = 0.016). Conclusion: The missense variant rs6923761 in the GLP1R gene was associated with a smaller glycemic response to 6 month gliptin therapy in diabetic patients of central European origin.
Keywords: DPP4 inhibitors; GPL1R; genetic variant; gliptins; glycated hemoglobin; pharmacogenetics; type 2 diabetes.