Network meta-analysis of 2,937 patients: obicetrapib outperforms anacetrapib on LDL-C, HDL-C and overall adverse events (Daru 2026)

Background: Cholesteryl ester transfer protein (CETP) inhibitors, specifically anacetrapib and obicetrapib, have shown strong lipid-modifying effects by lowering low-density lipoprotein cholesterol (LDL-C) and altering other lipid parameters. However, comparative evidence on their relative efficacy and safety is limited.

Objectives: To compare the efficacy and safety of anacetrapib and obicetrapib.

Methods: We systematically searched PubMed, Scopus, Web of Science, Cochrane Central Register, and ClinicalTrials.gov. The protocol was registered at OSF ( https://doi.org/10.17605/OSF.IO/VRP8Y ). The primary outcome was change in LDL-C; secondary outcomes included high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol, triglycerides, lipoprotein (a), apolipoprotein B (ApoB), apolipoprotein AI (ApoAI), apolipoprotein E (ApoE), incidence of adverse events, serious adverse events, and discontinuation. A frequentist random-effects network meta-analysis was performed using the netmeta package in R, with placebo as reference.

Results: Ten randomized controlled trials (2,937 patients) were included. Obicetrapib showed the most significant reduction in LDL-C (MD -33.63 mg/dL; 95% CI [-44.10, -23.16]) and the most significant increase in HDL-C (MD 154.33 mg/dL; 95% CI [132.73, 175.93]), outperforming anacetrapib. Both drugs comparably reduced non-HDL-C, ApoB, and Lp(a). Obicetrapib was associated with greater increases in ApoA1 and ApoE, while anacetrapib lowered triglycerides more effectively. Obicetrapib had the lowest risk of overall adverse events (RR 0.69; 95% CI [0.49, 0.99]) and ranked favorably for serious adverse events and discontinuation.

Conclusion: Both agents effectively reduced LDL-C levels, with obicetrapib demonstrating superior efficacy compared to anacetrapib. Additionally, both treatments demonstrated favorable safety profiles. These findings underscore the potential of CETP inhibitors as promising therapeutic options for patients with dyslipidemia.