How does SNAC affect Semaglutide  

Rybelsus (Main including Semaglutide and SNAC) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes on September 20, 2019.  

Rybelsus, developed by A Danish pharmaceutical company and Nord Ag, is the first drug approved in the United States for glucagon-like peptide-1 (GLP-1) receptor protein that does not require an injection.  

Rybelsus tablets contain 3mg,7mg, or 14mg Semaglutide and 300mg snac.3 mg as initial doses, which should be increased gradually as the body ADAPTS to actual needs, but at intervals of at least 30 days.

As an oral drug promoter, SNAC prevents the degradation of Semaglutide by pepsin by changing the PH value around the tablet and promoting the permeability of Semaglutide monomer through gastric mucosa.  

SNAC increases oral absorption of several co-administered poorly permeable molecules based on acid buffering, pepsin protection, and Semaglutide as monomer in the gastric presenting epithelium. In this study, it was proposed to replace SNAC with another PE analogue, which did not increase the flux of the gastric monolayer.  SNAC as the mechanism of action of Semaglutide stomach has been confirmed.  

In this study, rat mucous membranes were installed in a chamber and exposed to 10-30 mm SNAC. Semaglutide permeability increased 10 min after acute SNAC exposure, followed by removal of the SNAC buffer, and the effect gradually decreased at 30 and 60 min.  

In conclusion, SNAC forms a complex around Semaglutide in the stomach and causes a temporary increase in local PH around the molecule.  Semaglutide is said to be protected by SNAC against pepsin, and increased solubility leads to an increase in concentration-dependent flux of Semaglutide through the gastric mucosa, using a cross-cellular mechanism, since the tablet is in close contact with epithelial cells.  By shifting the focus from conformational changes and increased lipophilicity to elevated stomach PH.  SNAC is thought to induce Semaglutide monomer production and increase gastric epithelial membrane fluidity without affecting tight junctions, allowing Semaglutide to cross cells into systemic circulation.  Part of SNAC’s role is to convert Semaglutide into a more permeable monomer form, and it performs better when formulated as a stomach-specific tablet.  

SNAC is  the most mature PE up to now. Maybe it is not the most efficient PE(often depending on the payload), but it has an excellent safety record, GRAS status, and can be manufactured in large quantities to good Manufacturing practice (GMP) quality.  

The approval of Rybelsus (oral Semaglutide) for the treatment of type 2 diabetes is considered a milestone in oral peptide delivery and encourages the use of preparations containing PE(SNAC) for other peptides.  

Currently ,Rybelsus has no universal alternatives. The most common Rybelsus has a minimum price of around 893.51USD, so it’s really expensive.  

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