Hormonal
Biased agonism of GLP-1R and GIPR (favoring cAMP over beta-arrestin recruitment) yields superior glucose lowering, food intake suppression, and weight loss compared to unbiased agonism.
Current GLP-1/GIP drugs that favor cAMP signaling (biased) appear to offer better and longer-lasting glucose control and weight loss than those that do not. This is likely due to the drug staying on the receptor longer without being internalized. While this is proven in mice, it suggests that drug design matters for efficacy, not just receptor activation.
Biased GLP-1R and GIPR agonism leads to better and prolonged glucose lowering, greater food intake reduction, and weight loss than unbiased agonism.
Why this rating
High-quality in vivo animal studies with rigorous controls and mechanistic validation, though not yet human clinical data.
Source
Biased agonism of GLP-1R and GIPR enhances glucose lowering and weight loss, with dual GLP-1R/GIPR biased agonism yielding greater efficacy
Rubén Rodríguez et al. · Cell Reports Medicine · 2025
DOI 10.1016/j.xcrm.2025.102156
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