Obicetrapib
Network meta-analysis of 9,248 patients ranks obicetrapib plus ezetimibe plus statin best overall, obicetrapib plus statin safest among CETP-inhibitor combinations (J Cardiovasc Pharmacol 2026)
Original title: Lipid-Lowering Efficacy and Adverse Events of CETP Inhibitor Combination Therapy: A Systematic Review and Network Meta-Analysis
A systematic review and network meta-analysis of 13 randomised controlled trials (9,248 participants) comparing CETP-inhibitor-based combination therapies. Obicetrapib plus ezetimibe plus statin ranked highest for HDL-C elevation (SUCRA 95.1%), total cholesterol reduction (SUCRA 100.0%), triglyceride reduction (SUCRA 99.9%) and apoB reduction (SUCRA 100.0%), while evacetrapib plus statin ranked best for LDL-C reduction (SUCRA 94.3%). Obicetrapib plus statin had the best safety profile for all-grade and severe adverse events (SUCRA 19.2% and 22.5%), whereas evacetrapib plus statin had the worst (SUCRA 83.1% and 66.3%). The authors conclude the triple obicetrapib-ezetimibe-statin regimen gives the best comprehensive efficacy and obicetrapib-statin the best safety, an indirect ranking pending head-to-head confirmation.
Original abstract
Background: The therapeutic effects of different combination therapies containing cholesteryl ester transfer protein (CETP) inhibitors vary. Evidence from head-to-head comparisons is scarce and inconsistent. This study aimed to evaluate the impact of CETP inhibitor-based combination therapy on lipid levels and explore its adverse events (AEs).
Method: Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane Library, and Web of Science up to August 30, 2025. Thirteen RCTs were analyzed through STATA 14.0.
Results: This systematic review and network meta-analysis of 13 studies (9248 participants) evaluated CETP inhibitor-based combination therapies. For HDL-C elevation, obicetrapib + ezetimibe + statin ranked highest (SUCRA = 95.1%). Evacetrapib + statin achieved reduction in LDL-C (SUCRA = 94.3%). Obicetrapib + ezetimibe + statin excelled in reducing TC (SUCRA = 100.0%) and TG (SUCRA = 99.9%). Obicetrapib + statin was most effective for ApoAI increase (SUCRA = 100.0%), while obicetrapib + ezetimibe + statin best reduced ApoB (SUCRA = 100.0%). Regarding safety, obicetrapib + statin had the optimal profile for all grade AEs (SUCRA = 19.2%) and severe AEs (SUCRA = 22.5%), conversely, evacetrapib + statin had the worst profile (SUCRA = 83.1% and 66.3%, respectively).
Conclusions: Our meta-analysis demonstrated that CETP inhibitor combination therapies offer distinct lipid-modulating benefits and safety profiles. The obicetrapib + ezetimibe + statin triple therapy showed superior comprehensive efficacy, while obicetrapib + statin exhibited the optimal safety. Evacetrapib + statin provided potent LDL-C reduction but had the poorest safety. These findings facilitate personalized treatment selection for dyslipidemia management.
Trial Registration: PROSPERO CRD420251145396 ( https://www.crd.york.ac.uk/prospero/ ).
the classevacetrapibezetimibeobicetrapibstatins
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.