Torcetrapib
A Nature Reviews Drug Discovery analysis asks whether the torcetrapib failure means functional quality of HDL matters more than its circulating quantity (Nat Rev Drug Discov 2008)
Original title: Is raising HDL a futile strategy for atheroprotection?
The dramatic failure of clinical trials evaluating the CETP inhibitor torcetrapib cast considerable doubt on the value of raising HDL cholesterol as a cardiovascular treatment strategy. This review argues these results underscore the intricacy of HDL metabolism, suggesting that the functional quality of HDL particles may matter more than their circulating quantity, and that HDL-based therapeutics maintaining or enhancing HDL functionality warrant closer investigation. The authors review the complexity of HDL metabolism, examine clinical trial data for HDL-raising agents including possible explanations for the torcetrapib failure, and consider the outlook for future HDL-directed therapies.
Original abstract
The dramatic failure of clinical trials evaluating the cholesterol ester transfer protein inhibitor torcetrapib has led to considerable doubt about the value of raising high-density lipoprotein cholesterol (HDL-C) as a treatment for cardiovascular disease. These results have underscored the intricacy of HDL metabolism, with functional quality perhaps being a more important consideration than the circulating quantity of HDL. As a result, HDL-based therapeutics that maintain or enhance HDL functionality warrant closer investigation. In this article, we review the complexity of HDL metabolism, discuss clinical-trial data for HDL-raising agents, including possible reasons for the failure of torcetrapib, and consider the potential for future HDL-based therapies.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.