The class
Review asks whether CETP inhibitors are still worth pursuing after two decades of disappointing trials (Curr Atheroscler Rep 2022)
Original title: CETP Inhibitors: Should We Continue to Pursue This Pathway?
This review takes stock of more than two decades of pharmacological CETP inhibitor development, aimed at raising HDL cholesterol to prevent cardiovascular disease. Large clinical trials have repeatedly failed to reduce cardiovascular events, and the one programme that did show a cardiovascular risk reduction was halted for regulatory approval after causing adipose tissue accumulation. More recent observations suggest that lower CETP activity may prevent cardiovascular events through lipid lowering rather than HDL-cholesterol raising, and that CETP inhibitor treatment appears to beneficially affect glycaemic control in diabetes. The authors conclude these advances leave a potential path forward for CETP inhibitors in preventive cardiology, with implications for how future clinical development programmes should be designed.
Original abstract
Purpose Of Review: For more than 20 years there has been considerable interest in the development of pharmacological inhibitors of cholesteryl ester transfer protein (CETP) by virtue of their ability to raise levels of high-density lipoprotein cholesterol. This review endeavors to integrate existing data from prior clinical trials with emerging data to understand whether there is a pathway forward to develop CETP inhibitors to prevent cardiovascular disease.
Recent Findings: Large clinical trials have proved disappointing with successive reports of a failure to reduce cardiovascular events. The one clinical development program that did demonstrate a reduction in cardiovascular risk found adipose tissue accumulation and did not proceed for regulatory approval. More recent observations suggest that less CETP activity may prevent cardiovascular events, but due to lipid lowering rather than raising high-density lipoprotein cholesterol. In addition, treatment with CETP inhibitors appears to have a beneficial impact on glycemic control in the setting of diabetes. Advances in the field of CETP inhibition suggest a potentially protective effect on the risk of both cardiovascular disease and diabetes. This has implications for how to best design future clinical development programs and leaves the door open to potentially bring CETP inhibitors to the preventive cardiology clinic.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.