Paradoxically decreased HDL-cholesterol levels associated with rosiglitazone therapy.

Objective: To report 2 cases of very low high-density lipoprotein cholesterol (HDL-C) levels associated with rosiglitazone therapy.

Case Summary: Two patients with type 2 diabetes taking rosiglitazone for glycemic control developed paradoxically low HDL-C levels during rosiglitazone therapy. In the first patient, the HDL-C level decreased from 33 to 11.6 mg/dL after 8 months of therapy. The second patient's HDL-C level decreased from the baseline level of 44.8 mg/dL to 19.7 mg/dL after 4 months of rosiglitazone use. These abnormalities resolved on discontinuation of rosiglitazone and were not observed when the patients were treated with pioglitazone. The patients had no changes to other drug therapy or medical conditions known to affect lipid metabolism during treatment with rosiglitazone.

Discussion: Thiazolidinediones, insulin sensitizers widely used in the treatment of type 2 diabetes, have been reported to have beneficial effects on lipids, such as triglyceride lowering and HDL-C elevation, in addition to their glucose-lowering effects. It has been suggested that rosiglitazone and pioglitazone, the 2 currently available thiazolidinediones, may differ in their effects on lipids. As of July 2006, a total of 8 cases of paradoxical lowering of plasma HDL-C associated with rosiglitazone have now been reported. Based on use of the Naranjo probability scale, the 2 cases presented here were probably associated with rosiglitazone. The duration of therapy may be important in this paradoxical effect.

Conclusions: Rosiglitazone is associated with a paradoxical decrease in HDL-C levels in patients with type 2 diabetes. In patients receiving rosiglitazone, a baseline lipid panel should be performed and lipid values should be monitored during the course of therapy.