CETP inhibitors, state of the science: why torcetrapib, dalcetrapib, anacetrapib and evacetrapib failed and why obicetrapib is different (Curr Cardiol Rep 2026)

Original title: Cholesteryl Ester Transfer Protein Inhibitors: State of the Science

Curr Cardiol Rep · 6 January 2026 · 6

Nejabat M, Katsiki N, Mukherjee D, Hadizadeh F, Sahebkar A

A narrative review tracing why earlier CETP inhibitors failed to reach the market: toxic off-target effects and adverse cardiovascular signal for torcetrapib, neutral cardiovascular outcomes for dalcetrapib and evacetrapib, and insufficient effectiveness plus long half-life and fat accumulation for anacetrapib. Obicetrapib, an oral once-daily agent, is described as reducing LDL-C, non-HDL-C, apoB and Lp(a) while raising HDL-C and apoA-1, effective both alone and combined with statins with or without ezetimibe. The review notes computational approaches (QSAR modelling, molecular docking) aiding CETP inhibitor design, and flags the experimental compound MK-8262 as an early-stage candidate. A conceptual overview rather than new data, pending the ongoing obicetrapib trials.

Original abstract

PURPOSE OF REVIEW: Cholesteryl ester transfer protein (CETP) inhibitors are a promising class of drugs aimed at managing dyslipidemia by modulating lipoprotein levels, particularly low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), to mitigate cardiovascular (CV) risk. The main aim of this narrative review is to discuss the future of CETP inhibition. RECENT FINDINGS: Previous CETP inhibitors (namely, torcetrapib, dalcetrapib, anacetrapib and evacetrapib) failed to be commercialized due to toxic adverse events and negative CV effects (torcetrapib), neutral impact on CV outcomes (dalcetrapib and evacetrapib) and lack of effectiveness together with concerns on long half-life and accumulation in the fat (anacetrapib). Obicetrapib, a novel, oral, once-daily CETP inhibitor, has demonstrated significant efficacy in reducing LDL-C, non-HDL-C, apolipoprotein B (apoB) and lipoprotein (a) [Lp(a)] levels, while increasing HDL-C and apoA-1 levels. Clinical studies have shown its effectiveness both as monotherapy and in combination with statins ± ezetimibe, indicating enhanced lipid-altering efficacy and safety. Advances in computational modeling, such as QSAR models and molecular docking, have furthered the development of CETP inhibitors by predicting and enhancing their efficacy and selectivity. MK-8262 has shown some promise as a novel CETP inhibitor, but additional studies are indicated. This narrative review highlights the potential of obicetrapib in achieving lipid goals and better CV outcomes in various patient populations. The future of CETP inhibitors hinges on addressing past limitations, focusing on improving selectivity, exploring combination therapies, and employing personalized medicine approaches to maximize benefits while minimizing adverse effects. Furthermore, long-term safety studies, demonstrating cost-effectiveness, are crucial for regulatory approval and market acceptance. Such clinical trials are on-going with obicetrapib and their results, when available, will further elucidate its clinical implications/indications.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.