Despite standard lipid-lowering therapy, cardiovascular risk remains high in patients with hyperlipidemia. Obicetrapib, a novel inhibitor of cholesteryl ester transfer protein (CETP), may beneficially alter circulating lipoprotein concentrations.

We hypothesized that obicetrapib would reduce atherogenic lipid levels (LDL-C, non-HDL-C, Apo B, Lp(a), VLDL, triglycerides) and increase protective markers (HDL-C, Apo A1) compared with placebo.

We conducted a systematic review and meta-analysis of phase 2/3 randomized placebo-controlled trials of obicetrapib in adults with hyperlipidemia. Seven trials (N = 3,269) published through 2025 were identified. Pooled mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model; the I^2 statistic assessed heterogeneity while subgroup analyses compared obicetrapib doses plus ezetimibe regimens.

Obicetrapib significantly improved lipid profiles. LDL-C decreased markedly (MD –35.4 mg/dL), especially at higher doses, particularly with ezetimibe. Non–HDL-C similarly decreased (MD –27.2 mg/dL). Apolipoprotein B declined dose-dependently (MD –21.9 mg/dL), with significant reductions at 5 mg, 10 mg, and the highest effect with 10 mg plus ezetimibe (–10.9 mg/dL, –24.0 mg/dL, and –45.0 mg/dL, respectively). Lipoprotein(a) fell significantly, particularly at higher doses. HDL-C rose alongside apolipoprotein A1 (MD +51.3 mg/dL and MD +141.9 mg/dL, respectively). Triglycerides remained stable (MD +1.0 mg/dL), indicating a neutral effect, while VLDL modestly decreased at the lowest dose (MD –3.8 mg/dL).

Obicetrapib improved the lipoprotein profile, lowering atherogenic lipids and increasing HDL markers. Effects were dose-dependent and enhanced with ezetimibe. These findings support obicetrapib as an adjunct in hyperlipidemia therapy for optimal lipid management.