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The TRIUMPH-4 Phase 3 trial delivered headline weight loss numbers — 28.7% body weight reduction at the 12mg dose over 68 weeks — but it also surfaced a safety signal that did not show up cleanly in retatrutide's earlier Phase 2 data: dysesthesia

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The receptor's large, complex binding surface, characteristic of class B GPCRs, was thought to require the extensive contact area that only a peptide could provide