Evidence map›Paper›PMID 38316982›Full record

Trial reportNature metabolism2024

A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings.

Murielle M Véniant, Shu-Chen Lu, Larissa Atangan, Renee Komorowski, Shanaka Stanislaus, Yuan Cheng, Bin Wu, James R Falsey, Todd Hager, Veena A Thomas and 10 more

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04478708 (A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 133 in Subjects With Obesity), which is not on this map. Cited by 98 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 1 pooled it
60.1field-weighted citation impact, top 1% of its field
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.

NCT04478708 phase1completednot on this map

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 133 in Subjects With Obesity

TypeinterventionalSponsorAmgenRan2020 to 2022Enrolled110ConditionsObesityArmsmaridebart cafraglutide, Placebo
3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.

  1. Pooled it
  2. Glycemic and bodyweight effects ofScience advances · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026
    Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review

38 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

20 authors at 2 institutions in 1 country.

Murielle M Véniant *Amgen Research, Department of Cardiometabolic Disorders, Thousand Oaks, CA, USA. mveniant@amgen.com.ORCID http://orcid.org/0000-0002-1881-8252
Shu-Chen Lu *Amgen Research, Department of Cardiometabolic Disorders, Thousand Oaks, CA, USA.
Larissa AtanganAmgen Research, Department of Cardiometabolic Disorders, Thousand Oaks, CA, USA.
Renee KomorowskiAmgen Research, Department of Cardiometabolic Disorders, Thousand Oaks, CA, USA.
Shanaka StanislausAmgen Research, Department of Cardiometabolic Disorders, Thousand Oaks, CA, USA.
Yuan ChengAmgen Research, Department of Therapeutic Discovery, Thousand Oaks, CA, USA.
Bin WuAmgen Research, Department of Therapeutic Discovery, Thousand Oaks, CA, USA.
James R FalseyAmgen Research, Department of Therapeutic Discovery, Thousand Oaks, CA, USA.
Todd HagerAmgen Research, Department of Translational Safety & Bioanalytical Sciences, Thousand Oaks, CA, USA.
Veena A ThomasAmgen Research, Department of Pharmacokinetics and Drug Metabolism, South San Francisco, CA, USA.
Malhar AmbhaikarPre-pivotal Drug Substance Technologies, Amgen, Thousand Oaks, CA, USA.
Lucie SharpstenAmgen Early Development, Amgen, Thousand Oaks, CA, USA.
Yineng ZhuAmgen Early Development, Amgen, Thousand Oaks, CA, USA.
Vamsi KurraAmgen Research, Department of Translational Safety & Bioanalytical Sciences, Thousand Oaks, CA, USA.
Rohini JeswaniAmgen Research, Department of Translational Safety & Bioanalytical Sciences, Thousand Oaks, CA, USA.
Rajneet K OberoiAmgen Early Development, Amgen, Thousand Oaks, CA, USA.
Jane R ParnesAmgen Early Development, Amgen, Thousand Oaks, CA, USA.
Narimon HonarpourAmgen Early Development, Amgen, Thousand Oaks, CA, USA.
Joel NeutelOrange County Research Center, Tustin, CA, USA.
Jennifer L StrandeAmgen Early Development, Amgen, Thousand Oaks, CA, USA.
Amgen (United States) · USOrange County Research Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Obesity is a major public health crisis. Multi-specific peptides have emerged as promising therapeutic strategies for clinical weight loss. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are endogenous incretins that regulate weight through their receptors (R). AMG 133 (maridebart cafraglutide) is a bispecific molecule engineered by conjugating a fully human monoclonal anti-human GIPR antagonist antibody to two GLP-1 analogue agonist peptides using amino acid linkers. Here, we confirm the GIPR antagonist and GLP-1R agonist activities in cell-based systems and report the ability of AMG 133 to reduce body weight and improve metabolic markers in male obese mice and cynomolgus monkeys. In a phase 1, randomized, double-blind, placebo-controlled clinical study in participants with obesity ( NCT04478708 ), AMG 133 had an acceptable safety and tolerability profile along with pronounced dose-dependent weight loss. In the multiple ascending dose cohorts, weight loss was maintained for up to 150 days after the last dose. These findings support continued clinical evaluation of AMG 133.

Indexed as

Glucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorWeight LossAnimalsHumansMaleMiceObesityPeptidesGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorPeptides

Identifiers

PMID38316982
PMCPMC10896721
OpenAlexW4391533080

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.