Background: DPP-IV has a role in degradation of glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), and gastric inhibitory polypeptide (GIP) which had been reported to reduce bone resorption. We investigated the pharmacodynamic effect of evogliptin, a DPP-IV inhibitor, on human bone metabolism in human using serum carboxy-terminal collagen crosslinks (CTX) as a biomarker of bone resorption.
Method: This study was designed as a single institution, one sequence, single-dose, baseline comparative clinical trial. Serial blood samples were collected to quantify the concentrations of CTX), intact GIP, intact GLP-1, total GLP-2, PTH, osteocalcin were collected on Day 1 (baseline measurement day) and Day 2 (treatment day) during admission period. Urine samples for the quantification of deoxypyridinoline (uDPD) and creatinine (uCr) were also collected during the study. Paired t-test and McNemar test were applied in the hypothesis tests with a significance level of 0.05.
Results: Twenty-two menopausal women were enrolled and twenty subjects completed the study schedule. Serum CTX concentration significantly decreased at 2-8 hours after drug administration. Plasma intact GIP concentration significantly increased at 2-14 hours after drug administration, while plasma total GLP-2 concentration significantly decreased at 4-8 hours after drug administration. The levels of plasma intact GLP-1, PTH, osteocalcin, and uDPD/uCr were not significantly different between Day 1 and Day 2.
Conclusion: The study results suggests that the degradation of GIP might be more influenced by the DPP-IV activity compared to GLP-1 and GLP-2, and bone antiresorptive effect of evogliptin might be related to GIP rather than GLP-1 or GLP-2.