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Small Molecule Oral Agonists With Built-In Bias The oral nonpeptide GLP-1RAs orforglipron (Phase 3), CT-996 (Phase 1), and the investigational ASC30 are cAMP-biased by their binding mode as a structural consequence of their transmembrane domain binding geometry, which sterically limits -arrestin recruitment machinery coupling

also found that IC II activates the Keap1/Nrf2/GPX4 pathway to inhibit ferroptosis, reduce oxidative stress, and protect neural cells (Fan and Zhou, 2023)

Traditional bitters now studied for metabolic support include dandelion root, artichoke leaf, sweet wormwood, barberry, and bitter melon

This indicates that the benefit depends on GLP-1 signaling itself, rather than on unrelated metabolic changes