Hormonal
GIP receptor (GIPR) antagonism prevents diet-induced obesity and reduces fat mass in mice and non-human primates, independent of pancreatic beta-cell GIPR activity.
Blocking the GIP receptor appears to be a powerful strategy for weight loss in preclinical models, working by reducing food intake and increasing fat burning (lipid oxidation). This effect is independent of how the pancreas handles insulin, suggesting a direct metabolic benefit. When combined with existing GLP-1 drugs (like semaglutide or liraglutide), weight loss is significantly enhanced, suggesting these mechanisms can be stacked for greater efficacy.
GIPR knockout mice are protected against diet-induced obesity (DIO)... muGIPR-Ab protected against body weight gain, improved multiple metabolic parameters, and was associated with reduced food intake... In addition, we observed enhanced weight loss in DIO mice and NHPs when anti-GIPR antibodies were codosed with glucagon-like peptide-1 receptor (GLP-1R) agonists... we excluded the role of GIPR in pancreatic β-cells in the regulation of body weight and response to GIPR antagonism.
Why this rating
High-quality preclinical evidence (mouse and NHP models) with mechanistic validation (crystallography, conditional knockouts), but lacks human clinical trial data.
Source
Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models
Elizabeth A. Killion et al. · Science Translational Medicine · 2018
DOI 10.1126/scitranslmed.aat3392
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