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Cited by 10Lipoproteins and Cardiovascular HealthLipid metabolism and disordersCholesterol and Lipid Metabolism

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

Open access
Araújo, Beatriz, Arrighini, Giang Son, Queiroga, Flávia, Mansouri, Ensieh Sadat, Rivera, André, Amador, Wellgner Fernandes Oliveira, Queiroz, Ivo, Akabane, Maria Antônia Costa Cruz +5 more·2025·American Journal of Preventive Cardiology
DOI 10.1016/j.ajpc.2025.101303PMC PMC12528909
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Abstract

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. 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. 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; I 2 =64 %), lipoprotein(a) (MD: -37.16 %; 95 % CI: -43.63 to -30.70; p < 0.01, I 2 =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; I 2 =0 %), and triglyceride levels (MD: -7.21 %; 95 % CI: -11.13 to -3.30; p < 0.01; I 2 =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; I 2 =98.3 %), total cholesterol (MD: 11.94 %; 95 % CI: 5.61 to 18.28; p = 0.01; I 2 =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. 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.

AI snapshot

Written from the paper’s full text.

TL;DR

In an updated meta-analysis of 7 randomized controlled trials including 3381 participants, obicetrapib significantly lowered LDL-C, Lp(a), apoB, non-HDL-C, and triglycerides versus placebo, while increasing HDL-C, total cholesterol, and apolipoprotein A1. No significant differences in adverse events were observed, and obicetrapib was associated with lower new-onset diabetes risk.

Key findings

  • Obicetrapib reduced LDL-C by a mean difference of −37.21% (95% CI −41.53 to −32.90; p < 0.01; I²=64%), Lp(a) by −37.16% (95% CI −43.63 to −30.70; p < 0.01), apoB by −24.65% (95% CI −28.71 to −20.59; p < 0.01; I²=83%), non-HDL-C by −31.90% (95% CI −34.81 to −28.99; p < 0.01; I²=0%), and triglycerides by −7.21% (95% CI −11.13 to −3.30; p < 0.01; I²=0%).
  • Obicetrapib increased HDL-C by 142.17% (95% CI 117.56 to 166.78; p < 0.01; I²=98.3%), total cholesterol by 11.94% (95% CI 5.61 to 18.28; p = 0.01; I²=91%), and apolipoprotein A1 by 52.76% (95% CI 41.87 to 63.66; p < 0.01; I²=94%).
  • New-onset diabetes was lower with obicetrapib (RR 0.88; 95% CI 0.80 to 0.97; p = 0.01; I²=0%). There were no significant differences in any adverse events (RR 0.77; 95% CI 0.52 to 1.14; p = 0.19; I²=92%), trial agent-related adverse events (RR 0.93; 95% CI 0.67 to 1.29; p = 0.67; I²=10%), or cardiovascular adverse events (RR 0.82; 95% CI 0.58 to 1.16; p = 0.26; I²=0%).
  • A significant subgroup interaction by statin use was observed: LDL-C reduction was smaller with background statin therapy (MD −34.35%) than without statin use (MD −46.10%; p-interaction < 0.01). Meta-regression suggested greater LDL-C reduction in studies with higher baseline LDL-C.

Methods

  • Systematic review and meta-analysis of randomized controlled trials comparing obicetrapib versus placebo in adults with dyslipidemia and/or high cardiovascular risk; PubMed/MEDLINE, Embase, and Cochrane Central were searched from inception to June 2025.
  • Seven RCTs were included, comprising 3381 participants, of whom 2151 (63%) received obicetrapib; mean age was 64.3 years and 36% were women. For trials testing obicetrapib plus ezetimibe, only the obicetrapib monotherapy arm was included.
  • Random-effects Mantel-Haenszel models pooled risk ratios for binary outcomes and weighted mean differences for continuous outcomes; heterogeneity was assessed with Cochrane’s Q and I², with prespecified subgroup, leave-one-out sensitivity, and univariate meta-regression analyses. Risk of bias was assessed with RoB-2, and all included RCTs were rated low risk of bias.

Limitations

  • The paper states moderate heterogeneity, likely from differences in baseline lipid levels, background lipid-lowering therapies, and obicetrapib dosing; short follow-up periods limited assessment of long-term cardiovascular and safety outcomes; the small number of included studies prevented formal publication-bias evaluation with Egger’s regression test; and absence of patient-level data precluded granular subgroup assessment.
  • Evident from the text: heterogeneity was very high for some outcomes, including HDL-C (I²=98.3%), apoA1 (I²=94%), total cholesterol (I²=91%), any adverse events (I²=92%), and apoB (I²=83%).
  • Evident from the text: there are internal reporting inconsistencies, including R software version 4.4.2 in the abstract versus 4.5.0 in the methods, and Lp(a) I² reported as 48% in the abstract versus 55% in the results.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.ajpc.2025.101303

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

9 of 15 cited sources checked · 3 supported · 1 flagged · accuracy not yet measured

  • Interpretationcitation

    The finding of lower risk of new-onset diabetes with obicetrapib is consistent with previous mechanistic evidence linking CETP inhibition and HDL-C elevation to improved glucose metabolism.

    “This finding is consistent with previous mechanistic evidence linking CETP inhibition and HDL-C elevation to improved glucose metabolism [33,34].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [33] Drew, 2009, High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus, Circulation source

      The Clinical Perspective reports that short-term HDL elevation reduced plasma glucose through increased insulin and muscle glucose uptake. But the Clinical Implications section says no data had been published on the glucose-metabolic actions of CETP-inhibiting HDL-raising agents, so this paper does not provide mechanistic evidence for that part of the claim. Page numbers were not available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [34] Drew, 2012, The emerging role of HDL in glucose metabolism, Nat Rev Endocrinol source
  • Premisecitation

    Lowering LDL-C reduces the risk of major cardiovascular events.

    “Lowering low-density lipoprotein cholesterol (LDL-C) is a well-established strategy for reducing the risk of major cardiovascular events [1,2].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [1] Wang, 2022, Compounding benefits of cholesterol-lowering therapy for the reduction of major cardiovascular events: systematic review and meta-analysis, Circ Cardiovasc Qual Outcomes source
    • cites [2] Ference, 2017, Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel, Eur Heart J source
  • Findingown data

    Compared with placebo, obicetrapib significantly increased apolipoprotein A1 (MD: 52.76%; 95% CI: 41.87 to 63.66; p < 0.01; I2=94%).

    “apolipoprotein A1 concentrations (MD: 52.76 %; 95 % CI: 41.87 to 63.66; p < 0.01; I²=94 %; Supplemental Figure 2D)”
    Quote in the paperSubstantial claim
  • Findingown data

    Compared with placebo, obicetrapib significantly reduced mean LDL-C (MD: -37.21%; 95% CI: -41.53 to -32.90; p < 0.01; I2=64%).

    “Compared with placebo, obicetrapib significantly reduced mean LDL-C (MD: −37.21 %; 95 % CI: −41.53 to −32.90; p < 0.01; I2=64 %; Fig. 2A)”
    Quote in the paperSubstantial claim
  • Findingown data

    There were no significant differences in trial agent-related adverse events between obicetrapib and placebo (RR: 0.93; 95% CI: 0.67 to 1.29; p = 0.67; I2=10%).

    “trial agent-related adverse event (RR: 0.93; 95 % CI 0.67 to 1.29; p = 0.67; I2=10 %)”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 8
  • May combine two claims. 11

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Quality assessment of RCTs was performed using the Cochrane Collaboration's RoB-2 tool by two independent authors.

    “Quality assessment of RCTs was performed using the Cochrane Collaboration’s tool for assessing risk of bias in randomized trials (RoB-2) by two independent authors (M.A.C.C.A. and M.S.) [14].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [14] Sterne, 2016, ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions, BMJ source

      The Summary points distinguish the Cochrane risk-of-bias tool for randomised trials from the tool this paper describes: ROBINS-I, for non-randomised studies. This paper is therefore not a source identifying RoB-2, and it does not document the citing authors’ assessment by two independent reviewers. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Early generations of CETP inhibitors were either associated with off-target adverse effects with safety concerns, or had no significant or only modest LDL-C lowering and thus failed to demonstrate cardiovascular benefit.

    “Unfortunately, early generations of CETP inhibitors were either associated with off-target adverse effects with safety concerns, or had no significant or only modest LDL-C lowering and thus failed to demonstrate cardiovascular benefit, leading to a loss of enthusiasm in this drug class [[7], [8], [9], [10]].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [7] Barter, 2007, Effects of Torcetrapib in patients at high risk for coronary events, N Engl J Med source
    • cites [8] Schwartz, 2012, Effects of Dalcetrapib in patients with a recent acute coronary syndrome, N Engl J Med source

      The introduction (p. 2090) reports excess morbidity and mortality with torcetrapib associated with elevated aldosterone and blood pressure. The Discussion reports that dalcetrapib had minimal LDL-C effects and no significant cardiovascular benefit, but it does not establish that weak LDL-C lowering caused that outcome. It also cautions that the adverse effects observed across inhibitors may reflect CETP inhibition rather than drug-specific off-target effects. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [9] Lincoff, 2017, Evacetrapib and cardiovascular outcomes in high-risk vascular disease, N Engl J Med source

      The introduction (p. 1934) reports that torcetrapib was associated with suspected off-target toxicity and worse cardiovascular outcomes, while dalcetrapib had no effect on LDL cholesterol and did not reduce cardiovascular events. The paper does not say these results led to a loss of enthusiasm for CETP inhibitors. Its Discussion also reports that evacetrapib failed to improve outcomes despite substantial LDL-cholesterol lowering, so limited LDL lowering does not explain every failure it discusses. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The systematic review and meta-analysis were performed and reported following the Cochrane Collaboration Handbook for Systematic Reviews of Interventions and the PRISMA Statement guidelines.

    “The systematic review and meta-analysis were performed and reported following the Cochrane Collaboration Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement guidelines [12,13].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [12] Higgins J. Cochrane Handbook for Systematic Reviews of Interventions.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [13] Page, 2021, The PRISMA 2020 statement: an updated guideline for reporting systematic reviews, BMJ source

  • May combine two claims.

    Interpretationown data

    The addition of obicetrapib resulted in an incremental LDL-C reduction of approximately 34%, exceeding the typical benefit achieved with ezetimibe.

    “The addition of obicetrapib resulted in an incremental LDL-C reduction of approximately 34 %, exceeding the typical benefit achieved with ezetimibe.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [23] Cannon, 2015, Ezetimibe added to Statin therapy after acute coronary syndromes, N Engl J Med source

      The passage labeled CONCLUSIONS reports that ezetimibe added to statins lowers LDL cholesterol by an additional 23–24% on average, supporting the ezetimibe benchmark. The paper studies ezetimibe, not obicetrapib, and does not support the claimed 34% reduction with obicetrapib. No page number is available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Each 40 mg per deciliter reduction in LDL-C is associated with approximately a 22% decrease in cardiovascular risk.

    “Each 40 mg per deciliter reduction in LDL-C is associated with approximately a 22 % decrease in cardiovascular risk [3].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [3] Baigent, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials, Lancet L Engl source

  • May combine two claims.

    Interpretationcitation

    Obicetrapib was associated with a 37% reduction in Lp(a) levels, which is higher than the average reduction of 27% observed with PCSK9 inhibitors.

    “Obicetrapib was associated with a 37 % reduction in Lp(a) levels, which is higher than the average reduction of 27 % observed with PCSK9 inhibitors [29].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [29] Rivera, 2025, Impact of proprotein convertase subtilisin/Kexin type 9 inhibitors on lipoprotein(a): a meta-analysis and meta-regression of randomized controlled trials, JACC Adv source

      The Results section (page unavailable) reports an average 27% reduction in Lp(a) with PCSK9 inhibitors compared with placebo or ezetimibe. The paper does not report a 37% reduction with obicetrapib, so it supports only the PCSK9-inhibitor portion of the comparison. (LLM, conf=0.89)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    The meta-analysis included 7 RCTs comprising 3381 participants, of whom 2151 (63%) received obicetrapib.

    “We included 7 RCTs comprising 3381 participants, of whom 2151 (63 %) received obicetrapib.”
    • Also stated in: § Study selection and characteristics · plain
      “Overall, 3381 individuals were included, of whom 2151 (63 %) were randomized to receive obicetrapib.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Omission of the TULIP trial nulled heterogeneity in LDL-C levels but had no impact on Lp(a) and HDL-C levels.

    “Omission of the TULIP trial nulled heterogeneity in LDL-C levels but had no impact on Lp(a), and HDL-C levels (Fig. 5).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Baseline LDL-C was 112 mg per deciliter, and baseline Lp(a) was 62 nmol/L.

    “Baseline LDL-C was 112 mg per deciliter, and baseline Lp(a) was 62 nmol/L.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The mean age of participants was 64.3 years, and 36% were women.

    “The mean age was 64.3 years, and 36 % were women.”
    • Also stated in: § Study selection and characteristics · hedged
      “Among participants with available data, mean age was 64.3 years, and 36 % were women.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Moderate heterogeneity was observed in the analysis, likely related to differences in baseline lipid levels, background lipid-lowering therapies, and obicetrapib dosing regimens across trials.

    “First, moderate heterogeneity was observed in our analysis, likely related to differences in baseline lipid levels, background lipid-lowering therapies, and obicetrapib dosing regimens across trials.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The prospective meta-analysis protocol was registered at PROSPERO (CRD420251074053).

    “The prospective meta-analysis protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251074053).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The small number of included studies prevented a formal evaluation of publication bias using Egger's regression test.

    “Third, the small number of included studies prevented a formal evaluation of publication bias using Egger’s regression test.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    No significant differences were observed in adverse events, supporting the favorable safety profile of obicetrapib.

    “No significant differences were observed in adverse events, supporting the favorable safety profile of obicetrapib.”
    • Also stated in: § Conclusion · plain
      “There were no differences in adverse events between groups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Two authors independently screened titles and abstracts and evaluated the articles in full for eligibility based on prespecified criteria, with disagreements resolved in a panel discussion.

    “Two authors (E.S.M. and G.S.A.) independently screened titles and abstracts and evaluated the articles in full for eligibility based on prespecified criteria, disagreements were resolved in a panel discussion between authors.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Three large-scale phase 3 randomized controlled trials (TANDEM, BROADWAY, and BROOKLYN) have been published, collectively enrolling over 3000 patients.

    “Since then, three large-scale phase 3 randomized controlled trials (RCTs), the TANDEM, BROADWAY, and BROOKLYN trials, have been published, collectively enrolling over 3000 patients [11].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Masson, 2025, Lipid-lowering efficacy of obicetrapib: a comprehensive systematic review and meta-analysis, J Clin Lipidol source
16 of 16

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Lp(a) heterogeneity differs between abstract and results

    Minor

    The abstract reports I2 of 48 % for Lp(a), while the results section reports 55 % for the same pooled effect.

  • Claim that all non-TULIP participants used statins conflicts with table

    Minor

    The text says all participants outside TULIP were on statins, but Table 1 reports statin use below 100 % in BROADWAY and TANDEM.

  • Different R versions reported

    Minor

    The abstract reports R version 4.4.2, whereas the statistical analysis section reports version 4.5.0.

3 of 3

Cites

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Cited by

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Authors
Araújo, B., Arrighini, G. S., Queiroga, F., Mansouri, E. S., Rivera, A., Amador, W. F. O., Queiroz, I., Akabane, M. A. C. C., Consoli, L. N., Sobral, M. V. S., Barbosa, L. M., Gioli-Pereira, L., & Michos, E. D.
Affiliations
  • Universidade Nove de Julho (BR)
  • University of Bologna (IT)
  • Emory University (US)
  • Tehran University of Medical Sciences (IR)
  • Universidade Federal de Campina Grande (BR)
  • University of Wisconsin–Madison (US)
  • Universidade Federal de Juiz de Fora (BR)
  • Universidade do Oeste Paulista (BR)
  • Universidade Federal de Minas Gerais (BR)
  • Johns Hopkins University (US)
Corresponding author
Araújo, Beatriz
ORCID
Venue
American Journal of Preventive Cardiology
Publisher
Elsevier BV
Published
2025-12
Volume
24
Pages
101303
ISSN
2666-6677 (ISSN-L)
DOI
10.1016/j.ajpc.2025.101303
PMC
PMC12528909
OpenAlex
W4415356168
Semantic Scholar
ab5779977b1de9b73cbc0963e70f484ca608d049
Cited by
10
References
32
Citations by year
2026: 9 · 2025: 1
FWCI
3.25
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Preventive Cardiology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
obicetrapib, CETP inhibitors, dyslipidemia, LDL cholesterol, lipoprotein(a), apolipoprotein B, non-HDL cholesterol, triglycerides, HDL cholesterol, new-onset diabetes, cardiovascular risk, lipid-lowering efficacy, drug safety, adverse events, cardiovascular outcomes, high cardiovascular risk patients, statin-sparing therapy, hypertriglyceridemia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-19.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-19.

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