ArticleNature metabolism2025
GIPR-Ab/GLP-1 peptide-antibody conjugate requires brain GIPR and GLP-1R for additive weight loss in obese mice.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed.
- A Sequential Dual GLP-1R/GIPR Agonist-To-Antagonist Molecule Achieves Superior Weight Loss in Obese Mice.Diabetes, obesity & metabolism · 2026Article
- Clinical Potential of GIP in Type 2 Diabetes and Obesity.Diabetes care · 2026Review
- Altered GScience advances · 2026Article
- Distinct brain regions mediate regulation of food intake in response to GIPR agonism or antagonism.Nature metabolism · 2026Article
- A Lineup for Next Anti-Obesity Medicines: Beyond Incretin-Based Pharmacotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 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
- Good things come in twos.Nature metabolism · 2026Article
- Advances in Therapeutic Antibody Discovery and Development Targeting G Protein-Coupled Receptors.Pharmacology research & perspectives · 2026Review
- The expanding landscape of GLP-1 medicines.Nature medicine · 2026Review
- Repurposing glucagon-like peptide-1 receptor agonists for the treatment of neurodegenerative disorders.Nature aging · 2026Review
- Glucagon-like peptide-1 medicines in neurological and psychiatric disorders.Cell reports. Medicine · 2025Review
- Downstream interaction by glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonism is required for synergistic effects on body weight.Molecular metabolism · 2025Article
- Review
- GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice.Nature metabolism · 2025Article
- The Premise of the Paradox: Examining the Evidence That Motivated GIPR Agonist and Antagonist Drug Development Programs.Journal of clinical medicine · 2025Review
- The Potential Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Glucose-Dependent Insulinotropic Polypeptide (GIP) Receptor Agonists in Obstructive Sleep Apnea and Obesity.Current pulmonology reports · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide 1 receptor (GLP-1R) are expressed in the central nervous system (CNS) and regulate food intake. Here, we demonstrate that a peptide-antibody conjugate that blocks GIPR while simultaneously activating GLP-1R (GIPR-Ab/GLP-1) requires both CNS GIPR and CNS GLP-1R for maximal weight loss in obese, primarily male, mice. Moreover, dulaglutide produces greater weight loss in CNS GIPR knockout (KO) mice, and the weight loss achieved with dulaglutide + GIPR-Ab is attenuated in CNS GIPR KO mice. Wild-type mice treated with GIPR-Ab/GLP-1 and CNS GIPR KO mice exhibit similar changes in gene expression related to tissue remodelling, lipid metabolism and inflammation in white adipose tissue and liver. Moreover, GIPR-Ab/GLP-1 is detected in circumventricular organs in the brain and activates c-FOS in downstream neural substrates involved in appetite regulation. Hence, both CNS GIPR and GLP-1R signalling are required for the full weight loss effect of a GIPR-Ab/GLP-1 peptide-antibody conjugate.
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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 Socratic graph.