Paradoxical HDL‐C reduction during rosiglitazone and fibrate treatment

Abstract

Dyslipidaemia in Type 2 diabetes mellitus (T2DM) is one of the major contributors in the pathogenesis of atherosclerosis. Thiazolidinediones (TZD), a class of drugs used in the treatment of T2DM, also modify lipids, especially lowering serum triglycerides and raising high-density lipoprotein cholesterol (HDL-C). We describe five patients taking rosiglitazone and a fibrate who showed a paradoxical fall in HDL-C, which would have been missed if HDL-C had not been routinely monitored. This could have had a major impact in increasing the cardiovascular risk in these patients. Our five patients showed marked variation in both the decrease in serum HDL-C (50-89%) and also in the time taken for recovery of HDL-C after withdrawal of rosiglitazone (between 5 and 20 weeks). Apolipoprotein A1 mirrored the drop in HDL-C in four of the five patients but in one subject this was not seen, suggesting the possibility of multiple mechanisms leading to the phenomenon described, perhaps involving HDL metabolism. Improvements in glycaemic control with rosiglitazone (absolute HbA(1c) reduction between 0.6 and 3.0%) were seen in four of our patients. This suggests that the peroxisomal proliferator-activated receptor gamma signalling pathways relevant to glucose homeostasis were intact. As atherosclerosis is associated with a decrease in the HDL-C level, our observations reinforce the message that HDL-C should be measured before and after the commencement of rosiglitazone and also on increasing the dosage