Semaglutide: from the molecule design to the STEP trials

Semaglutide is a long-acting GLP-1 receptor agonist, FDA-approved as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for weight management. Its development story is a good example of peptide engineering: a fatty-acid side chain binds albumin and gives it a week-long half-life. Key papers: 1. Knudsen & Lau (Front Endocrinol, 2019), on how semaglutide was discovered and developed. https://pubmed.ncbi.nlm.nih.gov/31031702/ 2. Buckley et al. (Sci Transl Med, 2018), on how the oral form gets absorbed in the stomach using the absorption enhancer SNAC. https://doi.org/10.1126/scitranslmed.aar7047 3. Wilding et al. (NEJM, 2021), STEP 1, the 68-week weight trial in adults without diabetes. https://doi.org/10.1056/NEJMoa2032183 For discussion: what does the STEP 1 extension data say about what happens after treatment stops? The full write-up is in Guides: Semaglutide.