Evidence mapPaperPMID 41941715Full record

ArticleJournal of medicinal chemistry2026

Discovery of AMG 133, a Glucose-Dependent Insulinotropic Polypeptide Receptor Antagonist and Glucagon-Like Peptide 1 Receptor Agonist Antibody-Drug Conjugate for the Treatment of Obesity.

Bin Wu, James R Falsey, Chawita Netirojjanakul, Brad Herberich, Jerry Ryan Holder, Kelvin Sham, Jennifer Aral, Neil Forsythe, Kenneth W Walker, Shu-Chen Lu and 10 more

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

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

1 citing paper in PubMed.

  1. Review
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.

Bin WuTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.ORCID 0000-0002-5247-7332
James R FalseyTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Chawita NetirojjanakulTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Brad HerberichTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Jerry Ryan HolderTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Kelvin ShamTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Jennifer AralTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Neil ForsytheTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Kenneth W WalkerTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Shu-Chen LuDepartment of Cardiometabolic Disorders, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Todd HagerTranslational Safety & Bioanalytical Sciences, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Shanaka StanislausDepartment of Cardiometabolic Disorders, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Renee KomorowskiDepartment of Cardiometabolic Disorders, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Larissa AtanganDepartment of Cardiometabolic Disorders, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Michal AchmatowiczProcess Development, Amgen Inc. One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Dante RomaniniProcess Development, Amgen Inc. One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Dohan WeeraratneTranslational Safety & Bioanalytical Sciences, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Les P MirandaTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Murielle M VéniantDepartment of Cardiometabolic Disorders, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.
Yuan ChengTherapeutic Discovery, Amgen Research, One Amgen Center Dr, Thousand Oaks, California 91320, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multispecific therapeutics represent an increasingly important approach for enhancing the efficacy in complex diseases. Here, we report the design and optimization of novel antibody-peptide conjugates that combine glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonism with glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism for the treatment of obesity. A series of hybrid molecules was generated by conjugating synthetic GLP-1 peptides to IgG-based anti-GIPR antibodies, yielding markedly prolonged systemic exposure of the structurally intact GLP-1 peptide. In diet-induced obese mice and obese monkeys, once weekly administration of anti-GIPR-Ab/GLP-1 conjugates produced sustained body weight loss and improvements in metabolic parameters. This optimization effort culminated in the discovery of AMG 133, currently in phase III clinical trials with a profile that may support monthly dosing.

Indexed as

Anti-Obesity AgentsGlucagon-Like Peptide-1 Receptor AgonistsObesityReceptors, Gastrointestinal HormoneAnimalsDrug DiscoveryGlucagon-Like Peptide-1 ReceptorHumansMacaca fascicularisMaleMiceMice, ObeseAnti-Obesity Agentsgastric inhibitory polypeptide receptorGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsReceptors, Gastrointestinal Hormone

Identifiers

PMID41941715
PMCPMC13126679

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.