Thiazolidinediones, when used as monotherapy, are not associated with hypoglycemia, as they do not increase insulin secretion. Thiazolidinediones decrease the secretory demands and the strain on the b-cell caused by chronic insulin resistance and may preserve pancreatic b-cell function. Individuals using rosiglitazone or pioglitazone in combination with secretagogues or insulin therapy are at risk for hypoglycemic events.

In addition to their contribution as insulin sensitizers for glycemic control, the thiazolidinediones potentially have beneficial effects on endothelial function, atherogenesis, fibrinolysis, and ovarian steroidogenesis. Thiazolidinediones exhibit potent anti-inflammatory properties, and in recent clinical studies have been shown to retard the progression and reverse carotid intimal medial thickening, and decrease coronary intimal hyperplasia, in individuals with and without coronary stents. It remains unclear if these anti-inflammatory properties are unique to thiazolidinediones specifically or result from improvements in insulin resistance.

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