Evidence map›Paper›PMID 40640392›Full record

Trial reportNature medicine2025

Targeting the angiopoietin-like protein 3/8 complex with a monoclonal antibody in patients with mixed hyperlipidemia: a phase 1 trial.

Daniel Gaudet, Malgorzata Gonciarz, Xi Shen, Jennifer K Leohr, Thomas P Beyer, Jonathan W Day, Garrett R Mullins, Eugene Y Zhen, Maryalice Hartley, Miriam Larouche and 3 more

Registry-linked trialAbstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04052594 (A Randomized, Double-Blind, Single Dose, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3475766), which is not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04052594 phase1completednot on this map

A Randomized, Double-Blind, Single Dose, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3475766

TypeinterventionalSponsorEli Lilly and CompanyRan2019 to 2021Enrolled48ConditionsDyslipidemiasArmsLY3475766 - IV, LY3475766 - SC, Placebo - IV, Placebo - SC
3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Trial
  2. Review
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  5. Article
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  8. A neutralizing APOA5 monoclonal antibody reduces amounts of lipoprotein lipase in capillaries and triggers hypertriglyceridemia.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Article
  10. Article
  11. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Daniel GaudetDepartment of Medicine, Université de Montréal and ECOGENE-21, Saguenay, Quebec, Canada. daniel.gaudet@umontreal.ca.ORCID http://orcid.org/0000-0002-5185-3666
Malgorzata GonciarzLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Xi ShenLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Jennifer K LeohrLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0001-5434-7905
Thomas P BeyerLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0001-9153-6879
Jonathan W DayLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Garrett R MullinsLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.ORCID http://orcid.org/0009-0000-5320-1023
Eugene Y ZhenLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0002-0162-5665
Maryalice HartleyLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Miriam LaroucheDepartment of Medicine, Université de Montréal and ECOGENE-21, Saguenay, Quebec, Canada.
Robert J KonradLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Olivier BenichouLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Giacomo RuotoloLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA. ruotolo_giacomo@lilly.com.ORCID http://orcid.org/0000-0001-5247-5444

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The angiopoietin-like protein 3/8 complex (ANGPTL3/8) inhibits lipoprotein lipase (LPL) activity, primarily in oxidative tissues, and does so more potently than ANGPTL3, making ANPTL3/8 an attractive target for treating dyslipidemia. This study enrolled 48 adults (36 men, 12 women) with mixed hyperlipidemia to assess the primary outcome of safety and the secondary outcomes of pharmacokinetics and pharmacodynamics of ascending doses of LY3475766, a human monoclonal antibody that specifically blocks ANGPTL3/8-mediated inhibition of LPL activity. Participants received a single dose of LY3475766 or placebo. LY3475766 was well tolerated with no severe adverse events or adverse event-related discontinuations. Compared with placebo, LY3475766 dose-dependently reduced the concentration of triglycerides (-70%), remnant cholesterol (-86%), low-density lipoprotein cholesterol (-32%), non-high-density lipoprotein cholesterol (non-HDL-C) (-35%) and apolipoprotein B (-29%) while increasing HDL-C (+27%). LY3475766 thus significantly reduced atherogenic lipoprotein levels while increasing HDL-C levels; however, the effects on cardiovascular risk remain to be established. ClinicalTrials.gov registration: NCT04052594 .

Indexed as

AngiopoietinsAntibodies, MonoclonalHyperlipidemiasAdultAgedAngiopoietin-Like Protein 3Angiopoietin-Like Protein 8Angiopoietin-like ProteinsDouble-Blind MethodFemaleHumansLipoprotein LipaseMaleMiddle AgedPeptide HormonesTriglyceridesAngiopoietin-Like Protein 3Angiopoietin-Like Protein 8Angiopoietin-like ProteinsAngiopoietinsANGPTL3 protein, humanANGPTL8 protein, humanAntibodies, MonoclonalLipoprotein LipasePeptide HormonesTriglycerides

Identifiers

PMID40640392
PMCPMC12353791

What Socratic holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.