ArticleCell reports. Medicine2021
GIPR antagonist antibodies conjugated to GLP-1 peptide are bispecific molecules that decrease weight in obese mice and monkeys.
Article in Cell reports. Medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Efficacy of Glucagon-like Peptide-1 Receptor Agonists in Overweight/Obese and/or T2DM Adolescents: A Meta-analysis Based on Randomized Controlled TrialsJournal of clinical research in pediatric endocrinology · 2024Pooled it
- A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings.Nature metabolism · 2024Trial
- A Sequential Dual GLP-1R/GIPR Agonist-To-Antagonist Molecule Achieves Superior Weight Loss in Obese Mice.Diabetes, obesity & metabolism · 2026Article
- Review
- Multivalent antibody-based conjugates as new tools for tailored modulation of G protein-coupled receptors.British journal of pharmacology · 2026Review
- Clinical Potential of GIP in Type 2 Diabetes and Obesity.Diabetes care · 2026Review
- The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026Review
- Design and therapeutic rationale of antibody-peptide conjugates: insights from maridebart cafraglutide (AMG133) and emerging applications.Antibody therapeutics · 2026Review
- Advances in GLP-1 receptor agonists delivery systems for obesity and diabetes.Acta pharmaceutica Sinica. B · 2026Review
- 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.Journal of medicinal chemistry · 2026Article
- GIPR signaling modulates PYY-induced hypophagia and malaise in rodents.Molecular metabolism · 2026Article
- The role of GIP in carbohydrate metabolism: Implications in the development of therapies for T2DM, a narrative review.Histology and histopathology · 2026Review
- Spatially diffuse cAMP signalling with oppositely biased GLP-1 receptor agonists in β-cells despite differences in receptor localisation.Molecular metabolism · 2026Article
- Autoimmunity in MASLD: Focus on autoantibodies, anti-apolipoprotein A1 IgG and G protein-coupled receptors.European journal of clinical investigation · 2025Review
- Review
- GIP Receptor Antagonists in the Pharmacotherapy of Obesity: Physiologic, Genetic, and Clinical Rationale.Diabetes · 2025Review
- Hypophagia and body weight loss by tirzepatide are accompanied by fewer GI adverse events compared to semaglutide in preclinical models.Science advances · 2025Article
- GIPR-Ab/GLP-1 peptide-antibody conjugate requires brain GIPR and GLP-1R for additive weight loss in obese mice.Nature metabolism · 2025Article
- GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice.Nature metabolism · 2025Article
- Dual and Triple Gut Peptide Agonists on the Horizon for the Treatment of Type 2 Diabetes and Obesity. An Overview of Preclinical and Clinical Data.Current obesity reports · 2025Review
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) regulate glucose and energy homeostasis. Targeting both pathways with GIP receptor (GIPR) antagonist antibody (GIPR-Ab) and GLP-1 receptor (GLP-1R) agonist, by generating GIPR-Ab/GLP-1 bispecific molecules, is an approach for treating obesity and its comorbidities. In mice and monkeys, these molecules reduce body weight (BW) and improve many metabolic parameters. BW loss is greater with GIPR-Ab/GLP-1 than with GIPR-Ab or a control antibody conjugate, suggesting synergistic effects. GIPR-Ab/GLP-1 also reduces the respiratory exchange ratio in DIO mice. Simultaneous receptor binding and rapid receptor internalization by GIPR-Ab/GLP-1 amplify endosomal cAMP production in recombinant cells expressing both receptors. This may explain the efficacy of the bispecific molecules. Overall, our GIPR-Ab/GLP-1 molecules promote BW loss, and they may be used for treating obesity.
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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.