GLP-1 Receptor Agonists: Semaglutide
Semaglutide is the reference point for peptide delivery: an approved GLP-1 receptor agonist engineered for a one-week half-life by injection, and the first peptide of its class given orally, with SNAC, at about 0.4 to 1% bioavailability. Vegalab does not make or sell semaglutide; this page explains the delivery engineering behind it.
Molecule and mechanism
Semaglutide is a 31-amino-acid GLP-1 analog of about 4.1 kDa. Two changes extend its half-life to roughly one week: an Aib substitution at position 8 blocks DPP-4 cleavage, and a C18 fatty diacid on lysine 26 binds albumin, slowing renal clearance. It activates the GLP-1 receptor, increasing glucose-dependent insulin secretion, slowing gastric emptying and reducing appetite through central pathways. Albumin binding also creates a circulating reservoir that is released slowly, which reduces peak-to-trough variation between weekly doses.
Approved products
FDA-approved semaglutide products are Ozempic (weekly injection, type 2 diabetes, 2017), Rybelsus (daily oral tablet, type 2 diabetes, 2019) and Wegovy (weekly injection for chronic weight management, 2021). In December 2025 FDA approved an oral Wegovy tablet for chronic weight management. The EMA has authorized equivalent products. Semaglutide is not on the WADA Prohibited List. FDA has warned about unapproved and compounded products sold outside regulated channels. Vegalab does not supply any semaglutide product.
How oral semaglutide works
Rybelsus co-formulates semaglutide with sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC). In the stomach, SNAC raises local pH around the tablet, protecting the peptide from pepsin, and transiently increases transcellular permeability of gastric epithelium. Absorption is confined to the area around the eroding tablet, requires a fasting state and a small water volume, and still delivers well under 1% of the dose. The daily oral dose is therefore many times the weekly injected dose.
What this means for delivery research
Semaglutide shows that oral peptide delivery is achievable, and also what it costs: large amounts of drug, strict administration conditions and high variability between patients. Any new oral peptide approach should be benchmarked against this. The SNAC approach also shows the importance of local concentration: the enhancer works only near the tablet, which is why dosing conditions are strict. A particle-based system would need to recreate high local enhancer and peptide concentrations at the epithelium, rather than spreading both through the gut lumen. That is the specific design question a feasibility study must answer.
Key facts
- In STEP 1, weekly semaglutide 2.4 mg produced a mean 14.9% body weight reduction at 68 weeks versus 2.4% with placebo (Wilding et al. 2021, N Engl J Med 384:989)
- SNAC protects semaglutide from gastric degradation through a local pH buffering effect and enhances transcellular absorption in the stomach (Buckley et al. 2018, Sci Transl Med 10:eaar7047)
- Oral semaglutide bioavailability is approximately 0.4 to 1% (FDA label, Rybelsus 2019)
- Semaglutide half-life is approximately one week, supporting once-weekly injection (FDA label, Wegovy 2021)
How our delivery technology applies
Vegalab's interest is the delivery problem semaglutide exposes, not the molecule. A multi-layer particle could combine what SNAC does locally (pH shielding, permeation enhancement) with protease-resistant layers and mucoadhesion to hold the peptide at the epithelium for longer. That is a research hypothesis. Oral bioavailability of peptides remains typically under 1 to 2% even with the best enhancers, and we claim a program, not a result.
Pharma and biotech partners: discuss oral peptide feasibility with our delivery team.
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