Clinical trials with thiazolidinediones in subjects with Type 2 diabetes – is pioglitazone any different from rosiglitazone?

The thiazolidinediones, rosiglitazone and pioglitazone are used in the treatment of Type 2 diabetes (T2DM). Both have been shown to decrease glycated haemoglobin levels, fasting plasma glucose, insulin, and free fatty acids levels in subjects with T2DM. However, these agents have markedly different effects on lipids. Rosiglitazone increases total, low- and high-density lipoprotein (LDL and HDL) cholesterol, and triglycerides, whereas pioglitazone has no effect on total or LDL cholesterol, increases HDL cholesterol and decreases triglycerides. Both rosiglitazone and pioglitazone decrease inflammatory markers. Furthermore, both rosiglitazone and pioglitazone may cause a small decrease in blood pressure, improve endothelial function and reduce restenosis. Microalbuminuria is also reduced by both rosiglitazone and pioglitazone. Despite the improvements in surrogate end points, there is little clear evidence that either rosiglitazone or pioglitazone cause major improvements in cardiovascular outcomes. Thus, rosiglitazone has no effect or may even increase cardiovascular outcomes, whereas, in high-risk subjects, pioglitazone has a marginal ability to decrease cardiovascular outcomes. Unless the thiazolidinediones are shown to improve cardiovascular or other outcomes (e.g., renal) in the next few years, their continued use in T2DM should be questioned.