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Frisch, M

An oral supplement has to travel through your digestive tract, survive stomach acid, bind to a protein called intrinsic factor, and be absorbed in the small intestine

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The oral bioavailability of unmodified peptides is typically less than 1% due to proteolytic degradation and poor epithelial permeability. Mahato et al., Advanced Drug Delivery Reviews Why Peptides Are Hard to Deliver Orally Enzymatic breakdown: Peptidases in the GI tract cleave peptide bonds rapidly Low membrane permeability: Peptides are hydrophilic and large poor candidates for passive absorption First-pass metabolism: Even if absorbed, the liver may degrade peptides before they can exert any effect How Oral Peptide Delivery Is Improving Researchers are developing new technologies to overcome these barriers: Enteric coatings Protect peptides from stomach acid until they reach the small intestine Enzyme inhibitors Temporarily block proteases to allow peptides to survive longer Permeation enhancers Increase peptide absorption across the intestinal wall Peptide analogs Modified versions of natural peptides that resist degradation One example is oral semaglutide (GLP-1 agonist) the first FDA-approved peptide available in pill form for diabetes and weight loss