GRADE-assessed meta-analysis of 3,399 patients: obicetrapib raises the odds of reaching an LDL-C target under 55 mg/dL more than sixfold (Diabetes Obes Metab 2026)

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

Diabetes Obes Metab · 25 November 2025 · 7

Emara A, Gadelmawla AF, Awashra A, Rifai M, Elgendy MS, Diaa A, Emara M, Odat RM, Assaassa A, Shubietah A

A GRADE-assessed meta-analysis with trial sequential analysis of six randomised controlled trials (3,399 patients) testing obicetrapib at 1, 2.5, 5 and 10 mg in adults with dyslipidaemia, with or without atherosclerotic cardiovascular disease risk. At 8 to 12 weeks, obicetrapib reduced LDL-C by a mean difference of 27.66 mg/dL (26.96%, 95% CI, 21.70 to 33.62) and non-HDL-C by 35.41 mg/dL (28.08%), and raised HDL-C by 70.85 mg/dL (141.7%). It increased the likelihood of reaching LDL-C under 55 mg/dL (risk ratio 6.42, 95% CI, 5.15 to 8.01), under 70 mg/dL (risk ratio 2.56) and under 100 mg/dL (risk ratio 1.34), with no excess in total or serious adverse events. Short-term pooled trial data, with cardiovascular outcomes and durability still to be confirmed.

Original 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.

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