Stephen Buckley and colleagues have reformulated a prospective therapy for type 2 diabetes (T2D) now under clinical investigation as an oral treatment. Their modifications allowed the therapy to be effectively absorbed in the stomach - potentially offering patients a less invasive route of administration compared to the currently approved version of the therapy, which can only be dispensed by injection. Their research potentially expands the use of a T2D therapy that is now undergoing phase 3 clinical trials as an oral treatment. T2D affects over 30 million Americans, and one of the most successful T2D therapies involves a peptide hormone named GLP-1, which stimulates the release of insulin and maintains healthy blood sugar levels. Researchers have derived analogs of GLP-1 such as semaglutide that can lower blood sugar levels and blood pressure in T2D patients, but these peptides quickly break down in the gastrointestinal tract before they can be absorbed, limiting their route of administration to an injection. In an effort to offer clinicians greater treatment flexibility and improve T2D patient adherence to treatment programs, Buckley et al. created an oral formulation of semaglutide that was more readily absorbed. They designed and developed a tablet that contains both semaglutide and a fatty acid derivative named SNAC, which protected the semaglutide from being degraded by digestive enzymes. The authors then administered their tablet to dogs and humans and found it was absorbed by epithelial cells in the stomach rather than in the intestines, unlike most other drugs. The authors say that incorporating SNAC and similar compounds into oral peptide therapies could further boost their therapeutic potential.
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Journal
Science Translational Medicine