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Pioglitazone shows anti-inflammatory, anti-atherogenic effects  
  Carotid artery intima-media thickness (IMT) also was significantly reduced..
NEW YORK (Reuters Health) - Pioglitazone treatment improves several markers of cardiovascular risk in diabetic patients independent of its metabolic effects, a new study shows.
Animal research has suggested that thiazolidinediones, which act on the nuclear transcription factor peroxisome proliferator-activated receptor gamma, may have anti-inflammatory and anti-atherogenic properties, Dr. Andreas Pfutzner of the Institute for Clinical Research and Development in Mainz, Germany, and colleagues write in the June issue of the Journal of the American College of Cardiology.
To investigate whether these effects would be seen in humans as well, the researchers randomized 192 patients with type 2 diabetes to 45 mg of pioglitazone or 1 to 6 mg glimepiride daily. They measured several biochemical and clinical markers in the patients at study entry and six months later; 173 patients completed the study.
Patients on pioglitazone showed significant reductions in blood glucose, insulin and low-density lipoprotein to high-density lipoprotein ratio, and triglycerides compared to the glimepiride group. They also experienced a 29% decrease in high-sensitivity C-reactive protein (hsCRP) concentrations and a significant drop in matrix metalloproteinase 9 (MMM-9) and monocyte chemoattractant protein-1 (MCP-1) concentrations. Carotid artery intima-media thickness (IMT) also was significantly reduced. Increases in HDL and adiponectin also were seen among patients on pioglitazone, but not in those taking glimepiride.
Patients on glimepiride showed no reduction in hsCRP, MMM-9, MCP-1, or carotid artery IMT, the findings show. The two groups had similar reductions in HbA1c.
The decrease in IMT among patients on pioglitazone is the current study's "major clinical finding," Dr. Pfutzner and colleagues write, as carotid IMT thickness is "a strong and well described clinical predictor of cardiovascular risk and stroke." A prospective trial of pioglitazone in 5,238 patients with diabetes is underway, they continue, to investigate whether the drug can in fact help to prevent macrovascular events among patients at high risk.
J Am Coll Cardiol 2005;45:1925-1931.
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