Meta-analysis of 657 patients: obicetrapib combination therapy, especially with ezetimibe at 10mg, beats obicetrapib monotherapy for LDL-C lowering (Semergen 2026)

Original title: Systematic review and meta-analysis on the safety and efficacy of obicetrapib combination therapy in dyslipidemia

Semergen · 1 January 2026 · 6

Nawaz M, Hassan Zafar M, Ibrahim Smeak R, Rab Nawaz S, Ahmad B, Timsina G, Andleeb B, Waheed N, Hammad Arif M, Ahmad Khan U

A systematic review and meta-analysis of six randomised controlled trials (657 patients, LDL-C above 70 mg/dL) comparing obicetrapib combination therapy against obicetrapib monotherapy or placebo. The combination arm gave larger reductions in LDL-C (mean difference -44.14, 95% CI, -54.83 to -33.45), apoB (-28.94, 95% CI, -37.50 to -20.38) and non-HDL-C (-35.45, 95% CI, -48.46 to -22.45), and a greater HDL-C rise (149.15, 95% CI, 136.88 to 161.42). Adverse outcomes did not differ significantly. The 10 mg dose combined with ezetimibe gave the largest reductions, though the authors flag high heterogeneity across the pooled trials.

Original abstract

Aim: To evaluate the efficacy of obicetrapib combination therapy group against the obicetrapib alone or placebo arm.

Background: Recently, the drug obicetrapib has been explored as a combination therapy with other lipid-lowering therapies as a treatment option for dyslipidemia, with the potential to affect atherogenic lipoproteins.

Methods: This review registered with PROSPERO (CRD420251112605) included adult patients with LDL-C levels greater than 70mg/dl. A comprehensive search strategy was developed on PubMed, Cochrane Central and ClinicalTrials.gov to identify randomized controlled trial (RCT's). For risk of bias assessment, ROB 2.0 tool was used. The mean difference (MD) and risk ratio (RR) were calculated via a random effects model using RStudio version 4.5.1.

Results: We identified six RCT's with a total of 657 patients. LDL-C, Apo-B, and non-HDL-C were notably reduced in the obicetrapib combination therapy group, with MDs of -44.14 (95% CI: -54.83, -33.45), -28.94 (95% CI: -37.50, -20.38), and -35.45 (95% CI: -48.46, -22.45), respectively. Moreover, HDL-C levels were improved in the combination therapy group, with an MD of 149.15 (95% CI: 136.88, 161.42). The incidence of adverse outcomes was reported to be insignificant.

Conclusion: Our analysis revealed greater reductions in the levels of atherogenic lipoproteins, with obicetrapib combination therapies compared to placebo arm and obicetrapib monotherapy. A higher obicetrapib dosage (10mg), and combination with ezetimibe resulted in more reductions in lipoprotein levels. Although there is possibility for the effectiveness of obicetrapib combination therapies however due to high heterogeneity results needed to be interpreted with caution.

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