Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus--an effect probably mediated by direct platelet PPARgamma activation

Atherosclerosis. 2008 Apr;197(2):718-24. doi: 10.1016/j.atherosclerosis.2007.07.020. Epub 2007 Aug 31.

Abstract

Aims: Type 2 diabetes mellitus (T2DM) is associated with enhanced platelet activation. We conducted a randomised double-blind study to compare the effects of combination metformin and rosiglitazone or metformin and gliclazide therapy on platelet function in persons with T2DM.

Methods: Fifty subjects on metformin monotherapy received either rosiglitazone 4 mg or gliclazide 80 mg. HbA1c, HOMA-R, markers of platelet activation, inflammation, endothelial activation and oxidative stress were measured at baseline and after 24 weeks of treatment. Separate in vitro platelet function studies were conducted on platelets pre-incubated with rosiglitazone and gliclazide.

Results: A significantly greater reduction in platelet aggregation was observed in the rosiglitazone treated group compared to gliclazide. HbA1c and markers of endothelial activation were reduced to a similar extent in both groups. A significant reduction in HOMA-R, markers of inflammation and oxidative stress was only observed with rosiglitazone. Reduction in platelet aggregation with rosiglitazone correlated with reduction in oxidative stress. In the in vitro study, rosiglitazone produced significantly greater reduction in platelet aggregation compared with gliclazide.

Conclusion: Greater reduction in platelet activity observed with rosiglitazone may be related to reduced oxidative stress and a possible direct PPARgamma mediated effect on platelet function.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Blood Platelets / drug effects*
  • CD40 Ligand / drug effects*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Gliclazide / pharmacology*
  • Humans
  • Hypoglycemic Agents
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • PPAR gamma / drug effects
  • PPAR gamma / metabolism
  • Platelet Aggregation / drug effects*
  • Rosiglitazone
  • Thiazolidinediones / pharmacology*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • CD40 Ligand
  • Gliclazide