Updated meta-analysis of 3,381 patients: obicetrapib cuts LDL-C by 37% and, unexpectedly, new-onset diabetes by 12% (Am J Prev Cardiol 2025)

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

Am J Prev Cardiol · 17 September 2025 · 7

Araújo B, Arrighini GS, Queiroga F, Mansouri ES, Rivera A, Amador WFO, Queiroz I, Akabane MACC, Consoli LN, Sobral MVS, Barbosa LM, Gioli-Pereira L et al.

An updated meta-analysis of seven randomised controlled trials (3,381 patients, 63% on obicetrapib, mean age 64.3, 36% female) comparing obicetrapib with placebo in adults with dyslipidaemia or high cardiovascular risk. Obicetrapib reduced LDL-C by 37.21% (95% CI, 32.90 to 41.53), Lp(a) by 37.16%, apoB by 24.65%, non-HDL-C by 31.90% and triglycerides by 7.21%, while raising HDL-C by 142.17%, total cholesterol by 11.94% and apoA1 by 52.76%. Obicetrapib also reduced new-onset diabetes (risk ratio 0.88, 95% CI, 0.80 to 0.97), with no significant difference in adverse events. Pooled trial data with substantial heterogeneity on several endpoints; the diabetes signal is hypothesis-generating pending dedicated confirmation.

Original 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.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.