New Oral Delivery Technology Achieves Up to 15% Absorption of GLP-1 Peptide Drugs Through the Gut

The Axcess oral peptide delivery formulation achieved biopotencies of 9% for exendin-4 and 14.8% for semaglutide in preclinical models — meaning these percentages of the orally administered peptide reached the bloodstream in active form and produced measurable changes in insulin and glucose levels. The oral route delivers peptides to interact with GLP-1 receptors on vagal afferents in the intestine, mimicking how the body's own GLP-1 naturally works.

The Axcess oral peptide delivery formulation was tested with two GLP-1 receptor agonists (exendin-4 and semaglutide) in preclinical models. Oral administration was compared to injectable doses by measuring changes in blood insulin and glucose levels to determine biopotency (the fraction of orally delivered peptide that produces a biological effect equivalent to injection).

Most GLP-1 drugs require injection, which many patients dislike. While oral semaglutide (Rybelsus) exists, it requires high doses because very little peptide survives the digestive tract. Axcess technology achieves much higher oral bioavailability (14.8% for semaglutide vs ~1% for Rybelsus), which could enable lower oral doses, potentially reducing side effects and cost. More efficient oral delivery could make GLP-1 peptide therapy accessible to far more patients worldwide.

Oral peptide delivery is considered the holy grail of peptide therapeutics. While oral semaglutide proved the concept is viable, its ~1% bioavailability requires very high doses (14 mg oral vs 1 mg injectable). The Axcess platform's 14.8% biopotency represents a potential order-of-magnitude improvement that could reshape the GLP-1 drug market. If translated to humans, it could enable 1-2 mg oral doses — dramatically reducing costs and potentially improving tolerability.

These are preclinical data and oral bioavailability in humans may differ significantly. The specific animal models and detailed experimental conditions were not fully described in the abstract. Long-term safety of the Axcess formulation components was not addressed. Comparison with the existing oral semaglutide technology (SNAC enhancer used in Rybelsus) was not directly made. Manufacturing feasibility and stability of the formulation need evaluation.