Prediction of the effect on antihyperglycaemic action of sitagliptin by plasma active form glucagon-like peptide-1

AIM: To investigate whether active glucagon-like peptide-1 (GLP-1) is a prediction Factor of Effect of sitagliptin on patients with type 2 diabetes mellitus (GLP-1 FEST:UMIN000010645).METHODS: Seventy-six patients with type 2 diabetes,who had insufficient glycemic control [Hemoglobin A1c(HbA1c) ≥ 7%] in spite of treatment with metformin and/ or sulfonylurea, were included in the investigation. Patients were divided into three groups by tertiles of fasting plasma active GLP-1 level, before the administration of 50 mg sitagliptin. RESULTS: At baseline, body mass index, serum UA, insulin and HOMA-IR were higher in the high active GLP-1 group than in the other two groups. The high active GLP-1 group did not show any decline of HbA1c (7.6% ± 1.4% to 7.5% ± 1.5%), whereas the middle and low groups indicated significant decline of HbA1c (7.4 ± 0.7 to 6.8 ± 0.6 and 7.4 ± 1.2 to 6.9 ± 1.3, respectively) during six months.Only the low and middle groups showed a significant increment of active GLP-1, C-peptide level, a decreased log and proinsulin/insulin ratio after administration. In logistic analysis, the low or middle group is a significant explanatory variable for an HbA1c decrease of ≥ 0.5%,and its odds ratio is 4.5 (1.40-17.6) (P = 0.01) against the high active GLP-1 group. This remains independent when adjusted for HbA1c level before administration, patients’ medical history, medications, insulin secretion and insulin resistance.CONCLUSION: Plasma fasting active GLP-1 is an independent predictive marker for the efficacy of dipeptidyl peptidase 4 inhibitor sitagliptin.