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

The takeaway

The Axcess oral delivery platform achieved 14.8% biopotency for semaglutide — substantially higher than current oral formulations — potentially enabling lower-dose, more efficient GLP-1 pills.

14.8% oral biopotency for semaglutide
Compared to the roughly 1% absorption of current oral semaglutide (Rybelsus), this represents approximately a 15-fold improvement in oral peptide delivery efficiency.

What the researchers found

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.

Why it matters

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.

The numbers in context

Exendin-4: 9% oral biopotency · semaglutide: 14.8% oral biopotency · insulin and glucose changes measured · intestinal GLP-1R interaction via vagal afferents · Axcess™ formulation

How the study worked

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).

Who was studied

Preclinical animal models testing oral GLP-1 RA delivery with Axcess formulation

What this study cannot tell us

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.

How to read the evidence

This is a preclinical proof-of-concept study demonstrating enhanced oral peptide absorption. While the biopotency numbers are promising, validation in human pharmacokinetic studies is needed before drawing conclusions about clinical utility.

When this study was published

Published in 2024, this study represents current innovation in oral peptide delivery, addressing one of the biggest challenges in the rapidly growing GLP-1 drug market.

The bigger picture

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.

Questions still open

Does the 14.8% biopotency translate from preclinical models to human oral absorption?
How does Axcess compare head-to-head with the SNAC enhancer used in current oral semaglutide?
Could this technology enable oral delivery of other therapeutic peptides beyond GLP-1 agonists?

Common questions

Why is oral delivery of peptide drugs so difficult?

The digestive system is designed to break down proteins and peptides into individual amino acids for absorption. Any peptide drug taken orally gets attacked by stomach acid and digestive enzymes before it can reach the intestine. Even peptides that survive need to cross the intestinal wall to enter the bloodstream. Current oral semaglutide solves this partly with an absorption enhancer, but still achieves only about 1% bioavailability — meaning 99% of the drug is wasted.

How is the Axcess technology different from current oral semaglutide?

While exact details of the Axcess formulation aren't provided in the abstract, it achieves roughly 15 times higher peptide absorption than current oral semaglutide. It appears to enhance uptake through the intestinal wall while directing the peptide to interact with GLP-1 receptors on vagal nerve endings in the gut — the same way the body's natural GLP-1 works. This could mean lower doses are needed, potentially reducing both cost and side effects.

Read the original research

Glucagon-like peptide-1 receptor agonists for treatment of diabetes and obesity: advantage of oral delivery.

Frontiers in drug delivery, 4, 1456654

View on PubMed ↗Publisher’s paper ↗

Citation

New, R R C; Bogus, M; Travers, G N; Hahn, U; Vaiceliunaite, A; Burnet, M; Wang, J H; Wen, H. (2024). Glucagon-like peptide-1 receptor agonists for treatment of diabetes and obesity: advantage of oral delivery.. Frontiers in drug delivery, 4, 1456654. https://doi.org/10.3389/fddev.2024.1456654