Effects of thiazolidinediones on blood pressure

Peroxisome-proliferator-activated receptor-gamma (PPAR-gamma) agonists (known as thiazolidinediones; TDZs) activate nuclear receptors that regulate gene expression; they were developed as insulin-sensitizing drugs to treat type 2 diabetes mellitus. Although the prototypic TZD troglitazone was withdrawn from the market due to hepatic toxicity, rosiglitazone and pioglitazone are mainstays in managing type 2 diabetes mellitus. TZDs exert their hypoglycemic effect by reducing insulin resistance, hence improving insulin sensitivity. However, TZDs also exhibit a broad range of cardiovascular actions, with the clinical consequence of reduction in blood pressure (BP), observed in animal models and human diabetic subjects. The magnitude of reduction appears to be about 4 to 5 mm Hg in systolic and 2 to 4 mm Hg in diastolic BP--sufficient to significantly reduce subsequent cardiovascular event rates. But these BP-reducing properties, which are not present with metformin or sulfonylureas, are particularly important when viewed in conjunction with hypoglycemic effects. A significant proportion of patients with type 2 diabetes mellitus and BP mildly above target range might be successfully treated for both processes with a single drug.