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.

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.

• Authors: Koji Sakata, Manabu Hayakawa, Yuichiro Yano, Noboru Tamaki, Naoto Yokota, Takuma Eto, Reiko Watanabe, Naoteru Hirayama, Takeshi Matsuo, Kazuo Kuroki, Seiji Sagara, Osamu Mishima, Masahiro Koga, Naoto Nagata, Yuri Nishino, Kazuo Kitamura, Kazuomi Kario, Masayoshi Takeuchi, Sho-ichi Yamagishi
• Journal: Diabetes/metabolism research and reviews (Diabetes Metab Res Rev) Vol. 29 Issue 8 Pg. 624-30 (Nov 2013) ISSN: 1520-7560 [Electronic] England
• PMID: 23861159 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 John Wiley & Sons, Ltd.

Chemical References

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

Topics

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