Evidence map›Paper›PMID 40726454›Full record

Trial reportDiabetes, obesity & metabolism2025

Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids.

Yi Wen, Deven Lemen, Yanzhu Lin, Yan Q Chen, Ajit Regmi, William C Roell, Melissa K Thomas, Mark L Hartman, Tamer Coskun, Zvonko Milicevic and 3 more

Abstract readClinical Trial, Phase II
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Effect of Retatrutide, a Novel Triple Receptor Agonist, on Blood Pressure and Lipid Levels: A Systematic Review and Meta-analysis of Randomized Controlled Trials.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2026
    Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Review
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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.

Yi WenLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Deven LemenLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Yanzhu LinLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Yan Q ChenLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Ajit RegmiLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
William C RoellLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Melissa K ThomasLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.ORCID 0000-0001-9848-2834
Mark L HartmanLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Tamer CoskunLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.ORCID 0000-0002-2481-133X
Zvonko MilicevicLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.ORCID 0000-0002-6746-901X
Axel HauptLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.ORCID 0000-0003-4502-0470
Giacomo RuotoloLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.ORCID 0000-0001-5247-5444
Robert J KonradLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.ORCID 0000-0003-0923-0542

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThe aim of this study was to determine if retatrutide, a triple agonist of glucose-dependent insulinotropic polypeptide (GIP) receptor, glucagon-like peptide 1 (GLP-1) receptor and glucagon (GCG) receptor, may lower serum triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels in part by decreasing circulating concentrations of the angiopoietin-like protein 3/8 complex (ANGPTL3/8). MATERIALS AND

methodsIn post-hoc analyses of two phase 2 retatrutide trials, concentrations of ANGPTL3/8, ANGPTL4/8 complex (ANGPTL4/8), ANGPTL3 and ANGPTL4 were measured using dedicated immunoassays to determine percent changes from baseline. Correlations of ANGPTL protein and complex levels with lipid and metabolic parameters at baseline were analysed. Correlations of the changes in ANGPTL protein and complex levels versus the changes in lipid and metabolic parameters at study endpoints were also analysed. Direct effects of retatrutide itself, GIP, GLP-1, GCG and a GCG receptor (GCGR) antagonist antibody on ANGPTL3/8 secretion were studied in vitro using primary human hepatocytes.

resultsANGPTL3/8 reductions were observed with 8 and 12 mg retatrutide doses in participants with type 2 diabetes, and with 1, 4, 8 and 12 mg retatrutide doses in participants with obesity or overweight but without diabetes. In both cases, ANGPTL3/8 decreases paralleled retatrutide-induced reductions in TG and LDL-C. In primary human hepatocytes, both glucagon and retatrutide decreased ANGPTL3/8 secretion, and these reductions were blocked with the GCGR antagonist antibody.

conclusionsTogether, these results suggest that the GCGR agonism of retatrutide could lead to reduced circulating ANGPTL3/8 concentrations, which may then contribute to decreases in TG and LDL-C levels.

Indexed as

Angiopoietin-like ProteinsDiabetes Mellitus, Type 2Hypoglycemic AgentsPeptide HormonesAngiopoietin-Like Protein 3Angiopoietin-Like Protein 4Angiopoietin-Like Protein 8Cholesterol, LDLFatty AcidsFemaleGastric Inhibitory PolypeptideHumansMaleMiddle AgedPeptidesReceptors, Gastrointestinal HormoneAngiopoietin-Like Protein 3Angiopoietin-Like Protein 4Angiopoietin-Like Protein 8Angiopoietin-like ProteinsANGPTL3 protein, humanANGPTL4 protein, humanANGPTL8 protein, humanCholesterol, LDLFatty AcidsGastric Inhibitory Polypeptidegastric inhibitory polypeptide receptorHypoglycemic AgentsPeptide HormonesPeptidesReceptors, Gastrointestinal HormoneReceptors, GlucagonretatrutideTriglyceridesangiopoietin‐like protein (ANGPTL)glucagon (GCG)low‐density lipoprotein‐cholesterol (LDL‐C)retatrutidetriglycerides (TG)

Identifiers

PMID40726454
PMCPMC12409240

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Registered trials

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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 OpenQuestion graph.