Hormonal
A unimolecular antibody-peptide conjugate combining GIP receptor antagonism and GLP-1 receptor agonism (AMG 133) produces significant, sustained body weight loss in obese non-human primates when administered via once-weekly subcutaneous injection.
This research identifies AMG 133 as a potent obesity treatment in primates, achieving nearly 17% body weight loss with once-weekly injections. For humans, this suggests a future therapy that is more convenient than daily injections and potentially better tolerated than current single-target GLP-1 drugs, though it is not yet available for clinical use.
In the obese NHP model, four conjugates with hGIPR-Ab were studied, and conjugate 28 (AMG 133) demonstrated 16.9% weight loss compared to the vehicle group after 6 weeks of weekly subcutaneous dose at 0.75 mg/kg.
Why this rating
High-quality preclinical data in non-human primates (NHP) with chronic dosing, though human clinical trial results are not yet published in this specific text (only Phase III status mentioned).
Source
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 et al. · Journal of Medicinal Chemistry · 2026
DOI 10.1021/acs.jmedchem.6c00032
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