Efficacy and safety of obicetrapib in patients with dyslipidemia: An updated meta-analysis of randomized controlled trials

Beatriz Araújo; Giang Son Arrighini; Flávia Queiroga; Ensieh Sadat Mansouri; André Rivera; Wellgner Fernandes Oliveira Amador; Ivo Queiroz; Maria Antônia Costa Cruz Akabane; Leo N Consoli; Milene Vitória Sampaio Sobral; Lucas M Barbosa; Luciana Gioli-Pereira; Erin D Michos

doi:10.1016/j.ajpc.2025.101303

Efficacy and safety of obicetrapib in patients with dyslipidemia: An updated meta-analysis of randomized controlled trials

Am J Prev Cardiol. 2025 Sep 17:24:101303. doi: 10.1016/j.ajpc.2025.101303. eCollection 2025 Dec.

Affiliations

¹ Departament of Medicine, Nove de Julho University, São Bernardo do Campo, Brazil.
² University of Bologna, Bologna, Italy.
³ Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
⁴ Department of Medicine, University of Medical Sciences, Tehran, Iran.
⁵ Departament of Medicine, Federal University of Campina Grande, Cajazeiras, Brazil.
⁶ University of Wisconsin-Madison, Department of Radiology, WI, United States.
⁷ Departament of Medicine, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
⁸ Department of Medicine, Federal university of Bahia, Salvador, Brazil.
⁹ Departament of Medicine, University of Western, Presidente Prudente, Brazil.
¹⁰ Departament of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.
¹¹ Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil.
¹² Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Introduction: Obicetrapib is a novel cholesteryl ester transfer protein (CETP) inhibitor with promising lipid-lowering effects. While earlier CETP inhibitors have shown inconsistent cardiovascular outcomes and safety concerns, the efficacy and safety of obicetrapib remain under active investigation.

Methods: We systematically searched PubMed, Embase, and Cochrane Central databases for randomized controlled trials (RCTs) comparing obicetrapib versus placebo in adults with dyslipidemia or at high cardiovascular risk. We pooled mean differences (MDs) with 95 % confidence intervals (CI) with a random effects model. We used R software version 4.4.2 for statistical analysis.

Results: We included 7 RCTs comprising 3381 participants, of whom 2151 (63 %) received obicetrapib. The mean age was 64.3 years, and 36 % were women. Compared with placebo, obicetrapib significantly reduced mean LDL-C (MD: -37.21 %; 95 % CI: -41.53 to -32.90; p < 0.01; I²=64 %), lipoprotein(a) (MD: -37.16 %; 95 % CI: -43.63 to -30.70; p < 0.01, I²=48 %), apolipoprotein B (MD: -24.65 %; 95 % CI: -28.71 to -20.59; p < 0.01; I²=83 %), non-HDL-C (MD: -31.90 %; 95 % CI: -34.81 to -28.99; p < 0.01; I²=0 %), and triglyceride levels (MD: -7.21 %; 95 % CI: -11.13 to -3.30; p < 0.01; I²=0 %). Interestingly, obicetrapib also reduced the incidence of new-onset diabetes (RR: 0.88; 95 % CI: 0.80 to 0.97; p = 0.01; I²=0 %). In contrast, obicetrapib significantly increased HDL-C (MD: 142.17 %; 95 % CI: 117.56 to 166.78; p < 0.01; I²=98.3 %), total cholesterol (MD: 11.94 %; 95 % CI: 5.61 to 18.28; p = 0.01; I²=91 %), and apolipoprotein A1 concentrations (MD: 52.76 %; 95 % CI: 41.87 to 63.66; p < 0.01; I²=94 %). There were no significant differences in adverse events.

Conclusion: Among patients with dyslipidemia and/or high cardiovascular risk, obicetrapib significantly reduces LDL-C, lipoprotein(a), apolipoprotein B, and non-HDL-C. No significant differences were observed in adverse events, supporting the favorable safety profile of obicetrapib.

Keywords: CETP inhibitor; Dyslipidemia; LDL cholesterol; Lipoprotein(a); Obicetrapib.