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Many high-risk individuals fail to meet recommended LDL cholesterol targets, and up to 40% experience recurrent cardiovascular events, highlighting the need for novel interventions. This review consolidates the evidence from Phase I\u2013III trials (including TULIP, ROSE, BROADWAY, BROOKLYN and TANDEM) and meta-analyses. Take together, the results demonstrate that obicetrapib significantly reduces LDL cholesterol by 30\u201350%, apolipoprotein B by 20\u201330% and lipoprotein(a) by as much as 40-50%, while elevating HDL cholesterol levels by more than 100%. The average LDL cholesterol reduction was 0.92 mmol\/l (35.4 mg\/dl), with amplified effects when combined with ezetimibe. Obicetrapib achieves up to 97% inhibition of CETP activity and maintains a favourable safety profile. Additional metabolic benefits include decreased HbA1c and a lower incidence of new-onset diabetes. These results highlight obicetrapib\u2019s robust efficacy across multiple lipid parameters and its contribution to atherogenic lipoprotein reduction, particularly lipoprotein(a), a marker of high residual risk. Overall, obicetrapib represents a meaningful advancement in cardiovascular risk management and is positioned as an important new agent for high-risk patients with persistent residual risk despite current standard-of-care therapies.<\/jats:p>","DOI":"10.15420\/ecr.2025.88","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:45:10Z","timestamp":1790091910000},"source":"Crossref","is-referenced-by-count":0,"title":["Beyond Traditional Lipid Lowering: Obicetrapib and the Renaissance of Cholesteryl Ester Transfer Protein Inhibition"],"prefix":"10.15420","author":[{"given":"Prashant","family":"Thandi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00gvw6327","id-type":"ROR","asserted-by":"publisher"}],"name":"King George's Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2360-7580","authenticated-orcid":false,"given":"Akshyaya","family":"Pradhan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00gvw6327","id-type":"ROR","asserted-by":"publisher"}],"name":"King George's Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev","family":"Agarwala","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ec7xj20","id-type":"ROR","asserted-by":"publisher"}],"name":"Jaswant Rai Speciality Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raman","family":"Puri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Alfonso","family":"Perrone","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02p77k626","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Rome Tor Vergata"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6096","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"Mhaimeed O, Burney ZA, Schott SL, et al. 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