Safety and Efficacy of Obicetrapib for Atherogenic Lipid Reduction: A Systematic Review and Meta-Analysis

Cardiovascular risk remains elevated in hyperlipidemic patients despite standard lipid-lowering therapy, with dyslipidemia persisting as a key contributor. We conducted a meta-analysis to investigate the effectiveness and safety of obicetrapib, a selective cholesteryl ester transfer protein inhibitor, in improving lipid parameters and reducing residual cardiovascular risk in patients with dyslipidemia. The protocol of this meta-analysis was registered with PROSPERO (CRD420251102986). We searched MEDLINE (PubMed), Embase, the Cochrane Library, and trial registers from inception till July 2025 to identify randomized controlled trials investigating obicetrapib in adult patients with dyslipidemia. Our primary outcome was the mean percentage change from baseline in low-density lipoprotein cholesterol levels. Risk ratios and mean differences (MDs) were pooled under a random-effects model. Nine randomized controlled trials (n = 3516) were included in this review. Obicetrapib documented significant reductions in low-density lipoprotein cholesterol [MD: -37.45% (95% confidence interval (CI): -41.17 to -33.74)], apolipoprotein B [MD: -24.63% (95% CI: -28.42 to -20.84)], non-high-density lipoprotein cholesterol [MD: -30.96% (95% CI: -33.76 to -28.16)], triglyceride [MD: -7.5% (95% CI: -11.09 to -3.91)], and lipoprotein(a) [MD: -40.85% (95% CI: -54.79 to -26.90)] compared to placebo. High-density lipoprotein cholesterol levels significantly increased [MD: 150.06% (95% CI: 138.52-161.61)]. Obicetrapib was not associated with a significantly increased risk of adverse events compared to placebo. Obicetrapib significantly improved the lipid profile, with marked reductions in atherogenic lipoproteins and increases in HDL-related parameters with no major safety concerns observed. These results support the inclusion of obicetrapib in broader lipid management approaches aimed at reducing cardiovascular risk.