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

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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.