Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients

Diabetologia. 2005 Sep;48(9):1919-24. doi: 10.1007/s00125-005-1849-5. Epub 2005 Jul 9.


Aim/hypothesis: Evidence suggests that postprandial hyperglycaemia may be a cardiovascular risk factor in diabetes. Oxidative stress and inflammation are involved in the pathogenesis of diabetic complications and previous studies have shown increased oxidative stress and inflammation in the postprandial phase in diabetic patients. The aim of the present study was to evaluate whether controlling postprandial hyperglycaemia with S21403 (mitiglinide) is accompanied by a reduced generation of oxidative stress and inflammation.

Subjects and methods: Forty type 2 diabetic patients participated in the study. Two different breakfast-tests were performed in each patient, with placebo or S21403. Plasma nitrotyrosine, plasma malondialdehyde (MDA), oxidised LDL (oxLDL), plasma total radical-trapping antioxidant parameter (TRAP), IL-6, IL-18, TNF-alpha, plasma glucose and insulin were measured.

Results: After the administration of S21403, 40 mg, a rapid stimulation of insulin secretion was observed, accompanied by a reduction of postprandial hyperglycaemia. With S21403, a significant decrease of either nitrotyrosine, MDA and oxLDL levels, and a preservation of plasma TRAP compared with placebo was found. Significant decreases of IL-6, IL-18 and TNF-alpha were also observed with S21403 compared with placebo.

Conclusions/interpretation: This study shows that controlling postprandial hyperglycaemia with S21403 significantly improves the cluster of oxidative stress and inflammation markers that are increased in the postprandial state in diabetic patients.

Publication types

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

MeSH terms

  • Antioxidants / metabolism
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Indoles / therapeutic use*
  • Indoles / toxicity
  • Inflammation / prevention & control
  • Interleukin-18 / blood
  • Interleukin-6 / blood
  • Isoindoles
  • Oxidative Stress / drug effects*
  • Placebos
  • Postprandial Period
  • Tumor Necrosis Factor-alpha / metabolism


  • Antioxidants
  • Hypoglycemic Agents
  • Indoles
  • Interleukin-18
  • Interleukin-6
  • Isoindoles
  • Placebos
  • Tumor Necrosis Factor-alpha
  • mitiglinide