Obicetrapib for dyslipidemia with or without cardiovascular risk: A GRADE-assessed meta-analysis of randomized trials with trial sequential evidence

Affiliations

Advocate Illinois Masonic Medical Center

Abstract

Aims: Obicetrapib, an oral cholesteryl ester transfer protein (CETP) inhibitor, has demonstrated potent LDL-C lowering in recent phase 2/3 trials. We evaluated Obicetrapib (1, 2.5, 5, and 10 mg) efficacy and safety in adults with dyslipidemia, with or without atherosclerotic cardiovascular disease (ASCVD) risk.

Materials and methods: We performed a meta-analysis of randomized controlled trials (RCTs) identified through PubMed, Cochrane, Scopus, and Web of Science up to June 2025. Dichotomous outcomes were analyzed as risk ratios (RRs) and continuous outcomes as mean differences (MDs), both with 95% confidence intervals (CIs).

Prospero id: CRD420251107076.

Results: Six RCTs including 3399 patients were analysed. Compared with placebo, Obicetrapib significantly reduced LDL-C at 8-12 weeks (MD -27.66 mg/dL (-26.96%); 95% CI -33.62 to -21.70; p < 0.0001) and non-HDL-C (MD -35.41 mg/dL (-28.08%); 95% CI -39.42 to -31.39; p < 0.0001). It also increased HDL-C (MD 70.85 mg/dL (141.7%); 95% CI 62.56-79.15; p < 0.0001) and improved achievement of LDL-C targets: <55 mg/dL (RR 6.42; 95% CI 5.15-8.01), <70 mg/dL (RR 2.56; p < 0.0001), and < 100 mg/dL (RR 1.34; p < 0.0001). No significant differences were found in total adverse events (p = 0.41) or serious adverse events (p = 0.37).

Conclusion: Obicetrapib provides substantial improvements in lipid parameters with a favourable short-term adverse events rate. These results support its role as a potential adjunctive lipid-lowering agent irrespective of ASCVD risk. Longer-term trials are warranted to confirm its durability, cardiovascular outcomes, and safety.

Type

Article

PubMed ID

41287560

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