Pfützner A et al. (2005) Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the Pioneer study. J Am Coll Cardiol 45: 1925–1931

Results of the Pioneer study suggest that pioglitazone has anti-inflammatory and antiatherosclerotic effects, independent of glycemic control, which might be the direct result of peroxisome proliferative activated receptor gamma activation.

In this prospective open-label randomized trial, Pfützner and colleagues from Germany randomized 192 patients with type 2 diabetes to receive either pioglitazone 45 mg or glimepiride 1–6 mg, with the intention of achieving optimal glycemic control. Blood samples were assayed at baseline and after 6 months, to assess metabolic and cardiovascular markers. Carotid intima–media thickness was also measured.

A total of 173 patients (mean age 63 years; 107 male) completed the study. Glycated hemoglobin levels were comparable between treatment arms, but the pioglitazone arm showed statistically significant reductions in fasting glucose, insulin, LDL/HDL ratio, high-sensitivity C-reactive protein, matrix metalloproteinase 9, monocyte chemoattractant protein 1, and carotid intima–media thickness. These differences remained when the patient groups were stratified into therapy responders and nonresponders on the basis of their glycated hemoglobin levels, indicating that the reductions observed were independent of the improvement in metabolic control.

A larger study is underway to determine whether the improvements in surrogate markers seen with pioglitazone result in reductions in cardiovascular events for patients with diabetes.