CETP Renaissance with Obicetrapib.

PURPOSE OF REVIEW: This review examines the emerging role of cholesteryl ester transfer protein (CETP) inhibition, with a focus on obicetrapib, in lipid management and its potential implications beyond atherosclerotic cardiovascular disease (ASCVD), including neurodegeneration, glycaemic control, age-related macular degeneration (AMD), sepsis, and kidney function. RECENT FINDINGS: Obicetrapib is a potent, selective CETP inhibitor that overcomes the limitations of earlier agents, demonstrating substantial reductions in LDL-C, apolipoprotein B, non-HDL-C, and lipoprotein(a), alongside marked increases in HDL-C. Phase 2 and 3 trials confirm robust lipid-modifying efficacy and favourable safety. Emerging data suggest broader biological effects. Genetic and mechanistic studies link reduced CETP activity to improved brain structure and lower dementia risk, with biomarker analyses showing attenuation of Alzheimer’s disease-related markers, particularly in APOE ε4 carriers. Evidence further indicates potential metabolic benefits, including reduced risk of type 2 diabetes and improved glycaemic control. While genetic studies raise concerns about increased AMD risk, clinical trial data have not confirmed this association. Preclinical and human data suggest a protective role in sepsis via HDL-mediated endotoxin clearance, and early analyses indicate possible renal benefits through slower decline in kidney function. Obicetrapib represents a promising advancement in CETP inhibition, combining potent lipid-lowering effects with a good safety profile. Beyond cardiovascular risk reduction, emerging evidence supports potential roles in neurodegenerative disease, metabolic regulation, infection outcomes, and renal function. Ongoing outcome trials will determine its clinical impact and broader therapeutic relevance.