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Statements Author contributions LY: Software, Data curation, Investigation, Resources, Writing review & editing, Validation, Writing original draft, Visualization, Methodology

Tirzepatide 15 mg produced 5.5 kg more weight loss than semaglutide 1 mg (p 25,000 participants in the SURPASS and SURMOUNT programs [1, 2, 3]: Gastrointestinal effects (most common, dose-dependent): Nausea: 12-18% (5 mg), 15-22% (10 mg), 18-28% (15 mg) vs

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5c,d) or glucose deprivation-induced shYBX1 cell death (Extended Data Fig