Serum level of soluble CD26/dipeptidyl peptidase-4 (DPP-4) predicts the response to sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea

Dipeptidyl peptidase 4 (DPP-4) inhibitors is a new class of antihyperglycemic agents that is now available for the treatment of type 2 diabetes. We investigated the relationship between the baseline serum level of soluble CD 26/DPP-4 and the response to treatment with sitagliptin, a DPP-4 inhibitor, over 24 weeks in patients who had type 2 diabetes inadequately controlled by mefformin and/or sulfonylurea therapy. We studied 52 consecutive patients with type 2 diabetes who had poor glycemic control despite treatment with mefformin and/or sulfonylurea. All patients were given 50 mg/day of sitagliptin and were followed at monthly intervals for 24 weeks. Treatment with sitagliptin decreased significantly hemoglobin A1c (HbA1c) from 7.91 +/- 1.08% at baseline to 6.96 +/- 1.18% at 8 weeks, 7.04 +/- 0.77% at 16 weeks, and 7.08 +/- 0.80% at 24 weeks. The baseline serum level of sCD26 was correlated positively with HbA1c at both 16 weeks and 24 weeks. Furthermore, the serum sCD26 level at baseline was also correlated positively with the changes from baseline of HbA1c at 16 and 24 weeks (r = 0.318, P = 0.0296 and r = 0.516, P = 0.0003, respectively). In a multivariate logistic regression model that explained 56.1% (R(2) = 0.561) of the variation of the changes from baseline of HbA1c at 24 weeks, the baseline HbA1c (beta = -0.638, P < 0.001) and serum 5CD26 (beta = 0.357, P = 0.041) were independent determinants of the change of HbA1c at 24 weeks. In conclusions, a higher serum level of 5CD26 is associated with a worse response to sitagliptin in patients with type 2 diabetes controlled inadequately by mefformin and/or sulfonylurea therapy. (Translational Research 2012;159:25-31)