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GLP-1 receptor agonist molecules like semaglutide and tirzepatide are too large (4,100-4,800 daltons) to cross the skin barrier, which effectively blocks molecules above 500 daltons

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The table lists mild to moderate nausea in 40-50% of people as the expected gastrointestinal adjustment, and attributes the variation to gastric emptying rate, GIP receptor pathway sensitivity, and prior gastrointestinal tolerance

doi: 10.1038/nature12726 220 FurusawaYObataYFukudaSEndoTANakatoGTakahashiDet al