The class
Review highlights two small-molecule CETP inhibitors substantially raising HDL cholesterol in clinical trials (Curr Opin Cardiol 2005)
Original title: Drugs in development: targeting high-density lipoprotein metabolism and reverse cholesterol transport
This review summarizes currently available and emerging therapies for raising HDL cholesterol and targeting reverse cholesterol transport. It notes that recombinant apoA-I Milano/phospholipid complex infusions appeared to reduce atheroma volume by intravascular ultrasound, that intravenous and oral apoA-I mimetic peptides are in early clinical trials, and that next-generation PPAR-alpha agonists and dual PPAR-alpha/PPAR-gamma agonists are more potent HDL-raising agents than current fibrates. The review specifically highlights that two small molecule inhibitors of CETP have shown promise in clinical trials at substantially raising HDL cholesterol. The authors conclude that larger clinical trials with cardiovascular outcome measures are needed to assess these newer HDL-raising therapies.
Original abstract
Purpose Of Review: This review summarizes currently available therapies for raising high-density lipoprotein cholesterol (HDL-C) and expands on therapies currently in development that target high-density lipoprotein cholesterol.
Recent Findings: In the realm of new high-density lipoprotein-raising therapies, there is a strong focus on high-density lipoprotein metabolism and the reverse cholesterol transport pathway. Several infusions of recombinant apoA-I Milano/phospholipid complexes appeared to reduce atheroma volume as measured by intravascular ultrasound. Both intravenous and oral apoA-I mimetic peptides are in early clinical trials. Next generation PPAR-alpha agonists are more potent at high-density lipoprotein-raising than currently available fibrates, and dual PPAR-alpha/PPAR-gamma agonists are under investigation to help correct atherogenic dyslipidemia seen in many diabetics. Two small molecule inhibitors of the cholesteryl ester transfer protein have shown promise in clinical trials at substantially raising high-density lipoprotein cholesterol.
Summary: Larger scale clinical trials, including those with additional surrogate outcome measures as well as cardiovascular event outcomes are needed to further assess the benefit of newer high-density lipoprotein-raising therapies. Additional therapeutics are currently in development that target other parts of the reverse cholesterol transport pathway and, in addition to providing new potential pharmaceuticals, will help to further elucidate the atheroprotective mechanisms of high-density lipoprotein cholesterol.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.