The role of pioglitazone in modifying the atherogenic lipoprotein profile.

Pioglitazone, a thiazolidinedione, has established efficacy in improving glycaemic control in patients with type 2 diabetes. Pioglitazone also improves components of the mixed dyslipidaemia profile common in these patients, as typified by raised levels of plasma triglycerides, low levels of HDL cholesterol (HDL-C) and a raised proportion of LDL cholesterol (LDL-C) occurring as the small dense subfraction. In head-to-head trials, pioglitazone has consistently shown superior benefits on LDL-C and HDL-C as well as triglycerides compared with rosiglitazone and sulphonylureas. Pioglitazone used as monotherapy or combination therapy reduces levels of small dense LDL3 particles while raising levels of larger and less atherogenic LDL fractions. In addition, pioglitazone reduces cholesterol load and particle numbers of LDL3. Importantly, the differential effects of pioglitazone on LDL subfractions are complimentary and additive to those of simvastatin. Pioglitazone increases total HDL-C levels by 10-20%, mainly because of an increase in the larger HDL2 subfraction. Pioglitazone also significantly reduces plasma triglyceride levels by 10-25%. In recent studies, pioglitazone significantly reduced carotid and coronary atherosclerosis compared with the sulphonylurea glimepiride. The antidyslipidaemic effects of pioglitazone--in particular, improvements in HDL-C and reduction of small dense LDL3--may have contributed to these effects.