Rosiglitazone-Induced Severe Dyslipidemia

On rare occasions, initiation of the thiazolidinedione rosiglitazone may cause a profound decrease in HDL cholesterol and apoA1, with a concomitant increase in fasting triglycerides.

"This represents a potentially serious adverse event that requires detailed evaluation," Dr. Anita Sarker and colleagues from Addenbrooke’s Hospital in Cambridge write.

They describe three patients with type 2 diabetes and dyslipidemia in whom commencement of rosiglitazone was temporally related to a sharp decline in plasma HDL-C and apoA1, with a rapid return of HDL-C to pretreatment levels upon withdrawal of the drug.

Despite the exaggerated lipid response, all three patients experienced "striking improvement" in glycemic control with rosiglitazone.

Dr. Sarker’s team is aware of two other patients with similar responses to rosiglitazone initiation.

The mechanism of rosiglitazone-induced severe dyslipidemia remains to be determined, they note. Two of the patients were taking a fibrate when rosiglitazone was initiated and the third experienced further reductions in HDL-C when a fibrate was introduced, suggesting that coprescription of these two PPAR agonists might be involved.

Dr. Sarker feels that it is not clear how common this problem is, although, the fact that this phenomenon was not seen in greater than 1400 patients studied in clinical trials suggests that it is likely to be a rare side effect. However we would suggest that a full lipid profile that includes HDL-C should be measured before starting a thiazolidinedione and rechecked about 3 months after."

Diabetes Care 2004;27:2577-2580.