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A sensitized high-throughput screen identified a series of small molecule GLP-1R agonists that were optimized to promote endogenous GLP-1R signaling with nM potency

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Retatrutide's GCGR agonism is the most likely pharmacological explanation - glucagon has documented effects on sensory and autonomic nervous system function - and the dose-dependence (absent at lower doses, material at 9 and 12 mg) supports that hypothesis