Data alert

PROactive: The first prospective clinical outcomes trial of PPAR g agonists

Compared with the general population, persons with diabetes have a twofold greater absolute risk of cardiovascular (CV) disease.1 Studies have demonstrated that lowering glucose levels decreases microvascular complications such as retinopathy and nephropathy in these patients.2 However, with the exception of a subgroup of overweight patients with type 2 diabetes who received metformin in one trial, studies have failed to demonstrate any reduction in macrovascular complications, such as myocardial infarction (MI) and stroke.3 Very recently, the Diabetes Control and Complications Trial (DCCT) found that aggressive insulin treatment reduced risk of death, MI, or stroke by 57% in type 1 diabetes.4

Thiazolidinediones (TZDs), which activate peroxisome-proliferator-activated receptor g (PPARg), are among the newest class of treatment options that increase insulin sensitivity and lower plasma glucose levels.5 TZDs also exert a number of PPARg-mediated nonglycemic effects that may favorably impact the development and progression of atherosclerosis, including6,7:

  • Reduction in vascular inflammation
  • Decrease in levels of plasminogen activator inhibitor-1 (PAI-1)
  • Reduction in vascular smooth muscle cell migration and proliferation
  • Increase in HDL-C, often a decrease in triglycerides, and a shift in the distribution of LDL particle size, resulting in fewer small, dense particles
  • Reduction in blood pressure

The TZDs pioglitazone and rosiglitazone have been shown to blunt progression of carotid atherosclerosis.7-11 Observational data also suggest that TZDs may reduce the risk of MI in patients with diabetes.12 A number of prospective trials assessing the effect of pioglitazone and rosiglitazone on clinical outcomes are in progress. The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) is the first of these trials to be reported.13,14

Data_Alert.pdf (1.1MB)Data_Alert.pdf (1.1MB)

PROactive: Study design

Download VBWG06_DataAlert_PROactive.ppt (6 slides - 0.1MB)

PROactive: Study design PROactive: Baseline characteristics PROactive: CV medications at study entry PROactive: Reduction in primary outcome PROactive: Reduction in secondary outcome PROactive: Reduced need for insulin
References are listed at the end of the Data Alert.


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