Efficacy of alogliptin, a dipeptidyl peptidase-4 inhibitor, on glucose parameters, the activity of the advanced glycation end product (AGE) - receptor for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes

Diabetes Metab Res Rev. 2013 Nov;29(8):624-30. doi: 10.1002/dmrr.2437.

Abstract

Background: To examine the effects of alogliptin, a dipeptidyl peptidase-4 inhibitor, on glucose parameters, the advanced glycation end product (AGE)-receptor for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes patients.

Methods: Sixty-one patients whose HbAlc ≥ 6.1% (mean age 64.7 years; 67% men; mean HbAlc 7.4%; 57% were pharmacologically treated) underwent blood and urine sampling and analysis before and after 12 weeks of treatment with alogliptin (25 mg once daily).

Results: Alogliptin treatment significantly reduced fasting glucose (160.3 mg/dL at baseline versus 138.0 mg/dL at 12 weeks), glycoalbumin (21.1% at baseline versus 18.9% at 12 weeks), HbAlc (7.4% at baseline versus 6.9% at 12 weeks), circulating soluble form of RAGE concentrations (847.3 pg/mL at baseline versus 791.4 pg/mL at 12 weeks) and urine albumin to creatinine ratio (31.6 mg/g Cr at baseline versus 26.5 mg/g Cr at 12 weeks), whereas 1,5-anhydroglucitol concentrations were significantly increased (7.5 µg/mL at baseline versus 11.6 µg/mL at 12 weeks; all P < 0.05). Circulating AGEs concentrations were reduced only in patients with baseline AGEs ≥7 U/mL (n = 33, from 8.2 U/mL to 7.2U /mL; p < 0.01) after alogliptin treatment. The treatment-induced change of soluble form of sRAGE concentrations was associated with changes of 1,5-anhydroglucitol and HbAlc concentrations (rho = -0.32 and 0.29, respectively). Meanwhile, the treatment-induced change of urine albumin to creatinine ratio was associated with a change in the fasting glucose concentration (rho = 0.25; all p < 0.05). During the intervention, alogliptin treatment was well tolerated without any hypoglycemia or side effects.

Conclusion: Alogliptin treatment improved the AGE-RAGE axis and reduced albuminuria in Japanese type 2 diabetes patients.

Keywords: advanced glycation end products; albuminuria; alogliptin; receptor for advanced glycation end products; type 2 diabetes.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / drug effects
  • Humans
  • Male
  • Middle Aged
  • Piperidines / therapeutic use*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / drug effects*
  • Receptors, Immunologic / metabolism*
  • Uracil / analogs & derivatives*
  • Uracil / therapeutic use

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Piperidines
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • hemoglobin A1c protein, human
  • Uracil
  • alogliptin