Other Pharmacologic Approaches

In addition to the potential beneficial effect on restenosis described previously, TZD have shown antiinflammatory and anti-thrombotic properties in diabetes. From a clinical perspective, in the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROACTIVE) study, pioglitazone therapy in 5238 diabetic patients was associated with a nonsignificant 10% reduction in the primary end point (composite of all-cause mortality, nonfatal MI, stroke, ACS, endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle), compared with placebo. Allocation to piogli-tazone led to a significant 16% reduction in the main secondary end point (composite of all-cause mortality, non-fatal MI, and stroke).141 However, significantly more hospitalizations for heart failure were reported in the active treatment arm. More data will be available from BARI 2D ancillary studies, which will allow insights into the modulation of diabetes-associated inflammation, procoagulation, and progression of CAD mediated by insulin-sensitizing or insulin-providing regimens.73

Currently, there are two additional areas of strong interest in research/clinical application in the field of diabetes and cardiovascular disease. The first is optimization of blood glucose control, either by continuous insulin therapy and glycemic monitoring (closed loop) or by new therapeutic agents such as glucagon-like peptide-1 agonists and dipeptyl-peptidase-IV inhibitors. Second, endocannabinoid receptor antagonists have been shown to improve obesity and the overall cardiovascular risk profile. However, it remains to be determined whether these strategies may lead to a reduction in macrovascular or microvascular complications in diabetes.

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