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Gastrointestinal effects predominate: | Side Effect | Orforglipron | Oral Semaglutide | Tirzepatide | |-------------|-------------|-----------------|-------------| | **Nausea** | 22-28% | 24-28% | 24-31% | | **Vomiting** | 8-12% | 10-14% | 9-13% | | **Diarrhea** | 14-18% | 12-16% | 14-21% | | **Constipation** | 10-14% | 8-12% | 11-15% | | **Dyspepsia** | 6-9% | 8-11% | 5-8% | | **Discontinuation due to AEs** | ~6-8% | ~7-9% | ~4-7% | A notable difference: oral semaglutide has higher rates of upper GI symptoms (reflux, dyspepsia) because the SNAC formulation makes direct contact with gastric mucosa

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