The formulated MEDI7219 tablets require an enteric coating to protect the peptide from degradation in the stomach, thereby helping to ensure that the peptide and absorption enhancers reach the small intestine in proximity to each other for optimal absorption. Oral administration of hydrophilic macromolecules has been challenging primarily due to low intestinal epithelial permeability. Challenges usually come from passive or carrier-mediated transcellular permeation across phospholipid bilayers, as well as restricted paracellular transport via tight junctions. Propyl gallate (PG) has been used as a permeation enhancer excipient in several clinical trials . To increase oral bioavailability, the MEDI7219 peptide was formulated with a novel combination of excipients, with the primary permeation enhancers including PG . PG is the propyl ester of gallic acid and is a Generally Regarded As Safe (GRAS) compound used in foods, cosmetics and hair products at low levels . PG protects oils and fats in products from oxidation and has been added to foods containing oils and fats since 1948 . It is estimated that propyl gallate is used in over 150 cosmetic products at a maximum concentration of 0.1% . Free radicals of PG can inhibit the activity of enzymatic hydrolysis of adenosine triphosphate (ATP) . PG may also inhibit hepatic microsomal hydrolase and demethylase activities . As a food and cosmetic antioxidant, despite the presumed low toxicity, PG has been investigated to assess safety and various toxicological properties . The European Food Safety Authority has accepted a daily intake of 0.5 mg/kg body weight for this compound, primarily because of a gap in toxicity data more so than because of a specific safety concern. For a 60 kg individual, the proposed oral GLP-1 formulation would contain approximately 1.3-fold more PG than stipulated in these recommendations. Furthermore, the amount of PG planned for the MEDI7219 formulation is approximately 25-fold higher than in currently approved products in the United States [CDERs inactive ingredient database] . Early investigation regarding the toxicity profile of PG can be traced back to the 1980s and 1990s with focus on hepatic injury . These reports indicate that PG impairs mitochondrial function thus inducing cytotoxicity of hepatocytes.