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

Transl Res. 2012 Jan;159(1):25-31. doi: 10.1016/j.trsl.2011.09.005. Epub 2011 Oct 17.

Abstract

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 metformin and/or sulfonylurea therapy. We studied 52 consecutive patients with type 2 diabetes who had poor glycemic control despite treatment with metformin 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 (β = -0.638, P < 0.001) and serum sCD26 (β = 0.357, P = 0.041) were independent determinants of the change of HbA1c at 24 weeks. In conclusions, a higher serum level of sCD26 is associated with a worse response to sitagliptin in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea therapy.

MeSH terms

  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology
  • Dipeptidyl Peptidase 4* / blood
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hyperglycemia / drug therapy
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Metformin / pharmacology
  • Metformin / therapeutic use
  • Middle Aged
  • Pyrazines / pharmacology*
  • Pyrazines / therapeutic use
  • Sitagliptin Phosphate
  • Sulfonylurea Compounds / pharmacology
  • Sulfonylurea Compounds / therapeutic use
  • Time Factors
  • Triazoles / pharmacology*
  • Triazoles / therapeutic use

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Pyrazines
  • Sulfonylurea Compounds
  • Triazoles
  • Metformin
  • Dipeptidyl Peptidase 4
  • Sitagliptin Phosphate