Research ArticleDRUG MECHANISM

Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist

See allHide authors and affiliations

Science Translational Medicine  14 Nov 2018:
Vol. 10, Issue 467, eaar7047
DOI: 10.1126/scitranslmed.aar7047

Assisting absorption

Glucagon-like peptide-1 receptor agonists can help treat type 2 diabetes but must be administered by injection. Toward developing an effective oral therapy, Buckley et al. tested whether coformulating an oral GLP-1 analog, semaglutide, with SNAC, a small fatty acid derivative, improved drug absorption. Unlike most drugs, the coformulation was absorbed in the stomach rather than in the intestine. In animal studies and human trials, SNAC buffered the local pH of the stomach to protect against enzymatic degradation and facilitate transepithelial absorption via the transcellular route. These results suggest that the transient absorption enhancement offered by SNAC coformulation may help develop effective oral peptide–based therapies.

View Full Text

Stay Connected to Science Translational Medicine