Meta-analysis of three RCTs in 3,286 patients confirms obicetrapib effects on LDL-C, apoB and HDL-C with no excess adverse events (Ann Med Surg 2026)

Original title: Efficacy and safety of obicetrapib in patients at high cardiovascular risk: a systematic review, meta-analysis, and meta-regression

Ann Med Surg (Lond) · 17 June 2026 · 6

Kumar S, Sana Saeed S, Aftab Siddiqui T, Khan S, Saeed A, Khan M, Hanif H, Fasih A, Shabbir S, Basit A, Kumar L, Kumar H et al.

A systematic review and meta-analysis of three randomised controlled trials (n = 3,286) comparing obicetrapib 10 mg daily with placebo in adults with dyslipidaemia at high cardiovascular risk (established ASCVD, heterozygous familial hypercholesterolaemia, diabetes with added risk factors, or elevated LDL-C despite maximal statin therapy). Obicetrapib reduced LDL-C by a mean difference of 33.14 mg/dL (95% CI, 29.19 to 37.09), apoB by 20.25 mg/dL and non-HDL-C by 29.97 mg/dL, and raised HDL-C by 132.04 mg/dL. Adverse events (risk ratio 1.06) and serious adverse events (risk ratio 0.91) did not differ from placebo. A pooling of three already-published trials rather than new data, pending confirmation from a cardiovascular outcomes trial.

Original abstract

Background: Dyslipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C), is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Despite statin therapy, many patients fail to achieve target lipid levels or experience intolerance. Obicetrapib, a next-generation cholesteryl ester transfer protein inhibitor, has demonstrated potent lipid-modifying effects and favorable pharmacokinetics compared to its predecessors.

Objectives: To systematically review and meta-analyze randomized controlled trials (RCTs) evaluating the efficacy and safety of obicetrapib in patients with dyslipidemia at high cardiovascular risk.

Methods: A comprehensive search of PubMed, Medline, Cochrane Library, ScienceDirect, and ClinicalTrials.gov was conducted through June 2025. Eligible RCTs compared obicetrapib 10 mg once daily with placebo, reporting participants who were adults with dyslipidemia at high cardiovascular risk, defined as having established ASCVD, heterozygous familial hypercholesterolemia, diabetes mellitus with additional risk factors, or persistently elevated LDL-C despite maximally tolerated statin therapy. Data were pooled using random-effects models to calculate mean differences (MDs) for lipid parameters and risk ratios (RRs) for safety outcomes. Heterogeneity was explored via sensitivity and subgroup analyses.

Results: Three RCTs (n = 3286 participants) were included. Obicetrapib significantly reduced LDL-C (MD = -33.14 mg/dl; 95% CI: -37.09 to -29.19), ApoB (MD = -20.25; 95% CI: -23.25 to -17.25), non- high-density lipoprotein cholesterol (HDL-C; MD = -29.97; 95% CI: -33.24 to -26.69), triglycerides (MD = -7.56; 95% CI: -10.17 to -4.95), and increased HDL-C substantially (MD = +132.04 mg/dl; 95% CI: 124.82-139.26). The modest increase in total cholesterol was attributable to the elevation of HDL-C. No significant differences were observed in adverse events (RR = 1.06; P = 0.60) or serious adverse events (RR = 0.91; P = 0.36) compared with placebo.

Conclusion: Obicetrapib produces substantial, consistent improvements in atherogenic and anti-atherogenic lipid fractions without increasing adverse events. It holds promise as an adjunctive therapy for high-risk patients with residual dyslipidemia despite optimal statin therapy, pending confirmation from cardiovascular outcome trials.

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