Evidence map›Paper›PMID 38858523›Full record

Trial reportNature medicine2024

Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.

Arun J Sanyal, Lee M Kaplan, Juan P Frias, Bram Brouwers, Qiwei Wu, Melissa K Thomas, Charles Harris, Nanette C Schloot, Yu Du, Kieren J Mather and 2 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase II
In one paragraph

Trial report in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04881760 (A Phase 2 Study of Once-Weekly LY3437943 Compared With Placebo in Participants Who Have Obesity or Are Overweight With Weight-Related Comorbidities), which is not on this map. Cited by 160 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 6 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.

NCT04881760 phase2completednot on this map

A Phase 2 Study of Once-Weekly LY3437943 Compared With Placebo in Participants Who Have Obesity or Are Overweight With Weight-Related Comorbidities

TypeinterventionalSponsorEli Lilly and CompanyRan2021 to 2022Enrolled338ConditionsObesity, OverweightArmsLY3437943, Placebo
3 · Its place in the literature

Who cites it

160 citing papers in PubMed, 6 syntheses or guidelines 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
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  12. Inhibition of Acetylation Activity of p300/CBP Ameliorates Hepatic Steatosis Through Downregulation of ACSL4.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
  13. From Single Agents to Synergy: Redefining Therapeutic Strategies in MASLD.International journal of molecular sciences · 2026
    Review
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  18. MAFLD/MASLD: Past, Present, and Future.Journal of gastroenterology and hepatology · 2026
    Review
  19. Review
  20. The Evolution of Medications for Obesity Management.JGH open : an open access journal of gastroenterology and hepatology · 2026
    Review

100 more citing papers are in PubMed but not listed here.

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

12 authors.

Arun J SanyalStravitz-Sanyal Institute for Liver Disease and Metabolic Health and Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. arun.sanyal@vcuhealth.org.ORCID 0000-0001-8682-5748
Lee M KaplanSection of Obesity Medicine and Weight and Wellness Center, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Juan P FriasVelocity Clinical Research, Los Angeles, CA, USA.
Bram BrouwersEli Lilly and Company, Indianapolis, IN, USA.
Qiwei WuEli Lilly and Company, Indianapolis, IN, USA.
Melissa K ThomasEli Lilly and Company, Indianapolis, IN, USA.
Charles HarrisEli Lilly and Company, Indianapolis, IN, USA.
Nanette C SchlootLilly Deutschland GmbH, Bad Homburg, Germany.
Yu DuEli Lilly and Company, Indianapolis, IN, USA.
Kieren J MatherEli Lilly and Company, Indianapolis, IN, USA.
Axel HauptEli Lilly and Company, Indianapolis, IN, USA.
Mark L HartmanEli Lilly and Company, Indianapolis, IN, USA.ORCID 0000-0003-2396-7356

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 and glucagon receptors. A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and 12 mg, respectively. The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF. Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo. The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo). At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants. LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism. The ClinicalTrials.gov registration is NCT04881760 .

Indexed as

Fatty LiverAdultAgedDouble-Blind MethodFatty AcidsFemaleGlucagon-Like Peptide-1 Receptor AgonistsHumansLiverMaleMiddle AgedObesityPeptidesReceptors, GlucagonFatty AcidsGlucagon-Like Peptide-1 Receptor AgonistsPeptidesReceptors, Glucagonretatrutide

Identifiers

PMID38858523
PMCPMC11271400

What OpenQuestion 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 OpenQuestion graph.