Paradoxical severe decrease in high-density lipoprotein cholesterol due to rosiglitazone-fenofibrate interaction

Endocr Pract. May-Jun 2010;16(3):382-8. doi: 10.4158/EP09307.OR.


Objective: To determine whether the marked decrease in high-density lipoprotein cholesterol (HDL-C) occasionally associated with combination fibrate-thiazolidinedione therapy results from interaction between the 2 drugs or is solely the result of fibrate administration, a previously recognized cause.

Methods: We prospectively followed the clinical course of 2 patients receiving fenofibrate and rosiglitazone and reviewed the relevant literature, searching PubMed for reports describing striking reductions in HDL-C associated with fibrate administration alone and in conjunction with rosiglitazone and statins. Additional references were obtained from the bibliography of each identified article.

Results: Each of the 2 patients demonstrated a Drug Interaction Probability Score score of 9, indicating a highly probable likelihood of interaction. Critical review of all reported cases of concurrent fenofibrate-rosiglitazone-associated decreases in HDL-C failed to show conclusive evidence that the HDL-C decrease could be due to an interaction between the 2 drugs as opposed to either drug being given alone.

Conclusions: In at least some patients who experience marked HDL-C decrease when given a combination of fenofibrate and rosiglitazone, this severe adverse effect is the result of a drug interaction between the 2 pharmaceutical agents and is not reproduced by the administration of either drug singly.

MeSH terms

  • Aged
  • Cholesterol, HDL / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Interactions
  • Fenofibrate / adverse effects*
  • Fenofibrate / therapeutic use*
  • Humans
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use
  • Male
  • Prospective Studies
  • Rosiglitazone
  • Thiazolidinediones / adverse effects*
  • Thiazolidinediones / therapeutic use*


  • Cholesterol, HDL
  • Hypolipidemic Agents
  • Thiazolidinediones
  • Rosiglitazone
  • Fenofibrate