Lipid-Lowering Efficacy and Safety of Obicetrapib Alone and as an Add on Therapy: A Meta-Analysis of Randomized Controlled Trials

Obicetrapib is a cholesteryl ester transfer protein inhibitor that demonstrated reductions in atherogenic lipoproteins. We systematically searched PubMed, Scopus, and Clinicaltrials.gov for relevant randomized controlled trials from inception until September 2, 2025 to evaluate the efficacy and safety outcomes of obicetrapib as a standalone and add-on therapy. The mean difference (MD) with 95% confidence intervals (CI) was pooled using a random effects model. A total of 3512 patients were included. Obicetrapib significantly reduced low-density lipoprotein cholesterol [MD, -37.45 (95% CI, -43.76 to -31.15), P < 0.001], non-high-density lipoprotein (HDL) cholesterol [MD, -32.04 (95% CI, -38.49 to -25.60), P < 0.001], apolipoprotein B [MD, -24.71 (95% CI, -30.79 to -18.63), P < 0.001] and apolipoprotein A [MD, -39.10 (95% CI, -45.35 to -32.85), P < 0.001]. It significantly increased total cholesterol [MD, +10.41 (95% CI, 3.68-17.15), P < 0.001], HDL cholesterol [MD, +147.98 (95% CI, 129.23-166.54), P < 0.001], apolipoprotein A1 [MD, 55.54 (95% CI, 43.37-67.71)], and apolipoprotein E [MD, 53.24 (95% CI, 39.04-67.44), P < 0.001]. As an add-on therapy to ezetimibe, obicetrapib yielded greater reduction in low-density lipoprotein [MD, -51.99 (95% CI, -61.61 to -42.37), P < 0.001] and non-HDL [MD, -50.32 (-55.42 to -45.21), P < 0.001]. No significant effects were observed when combined with statins.