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Notably, the ferroptosis inhibitor Ferrostatin-1 exacerbated CGAs toxicity, while the inducer Erastin attenuated it (Supplementary Figure S2C), suggesting that the profound iron deficiency we describe disrupts fundamental metabolism in a manner distinct from, and prior to, the execution of classical ferroptosisa pathway CGA has been shown to inhibit in other contexts via Nrf2/GPX4 activation (Figures 5D,E), and a concentration of 800 M CGA induced significant ROS accumulation, activating the ROS-Erk1/2 stress pathway (Figure 7

The higher gastrointestinal adverse-event rate relative to semaglutide is the flip side of the greater weight loss and again points to escalation speed as a lever for tolerability

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