Thiazolidinediones, insulin resistance and obesity: finding a balance

The clinical efficacy of currently available thiazolidinediones (TZDs) in improving glycaemic control and ameliorating several risk factors for cardiovascular disease (linked to their insulin-sensitising actions as well as direct vascular effects) is well established. Treatment-associated weight gain, however, which has been identified as a class effect of the TZDs, is seen in a number of patients. The magnitude of weight gain correlates in part with improved metabolic control, i.e. better responders are more prone to increases in body weight. The cardiovascular risk associated with obesity appears to be depot specific; while peripheral obesity is associated with a low risk of cardiovascular complications, central obesity confers a greater degree of risk. Evidence is reviewed that increases in body weight associated with TZD treatment are associated with neutral effects (or even, decreases) in visceral fat, the adipose depot that is associated with central obesity.