Paradoxical fall in HDL cholesterol observed in a patient treated with rosiglitazone and pioglitazone

Abstract

Introduction Glitazones (also known as thiazolidinediones) are a class of drugs used to treat type 2 diabetes mellitus. They bind to and activate PPARγ, a ligand-activated nuclear transcription factor expressed in adipose tissue, endothelial cells, skeletal muscle liver cells and other tissues. The activated PPARγ leads to changes in expression/transcription of several genes involved in glucose and lipid metabolism. The two currently available glitazones, rosiglitazone and pioglitazone, have been shown to raise HDL-C and lower TG levels in several clinical studies as well as increasing insulin sensitivity. Separate meta-analyses of the effects of rosiglitazone and pioglitazone on cardiovascular events were reported in 2007. It was seen that while rosiglitazone appeared to be associated with an increased risk of myocardial infarction pioglitazone showed a beneficial effect. Although no explanation for these disparate observations has been provided the possibility of significant differences between the two glitazones exists. We recently reported five case studies in which the addition of rosiglitazone in patients already on a fibrate led to unexpected reductions in HDL-C but with improvements in glycaemic control. Although the reasons for this were not clear we suggested that thiazolidinediones cross-reacted with PPAR-α and either decreased synthesis of ApoA1 or increased catabolism of ApoA1 leading to lower levels of HDL-C. Three of the patients were switched from rosiglitazone to pioglitazone and the HDL-C returned to normal levels. This pointed to differences between the two drugs in their actions on lipid metabolism. We now report a case which showed a paradoxical decrease in HDL-C when treated with rosiglitazone, but unlike the other patients reported by us also demonstrated a similar change when switched to pioglitazone.