Oral GIP/GLP-1 Peptide Tablets Achieve Higher Bioavailability Than Oral Semaglutide in Monkeys | Research

The takeaway

Erodible tablets with SNAC permeation enhancer achieved 4.2% oral bioavailability for a GIP/GLP-1 dual agonist peptide — 3.5× higher than semaglutide (1.2%) — through improved pepsin stability and optimized release kinetics.

4.2% vs 1.2%
oral bioavailability of GIP/GLP-1 peptide vs semaglutide via SNAC tablets in monkeys

What the researchers found

GIP/GLP-1 dual agonist peptide with higher pepsin stability achieved 4.2% oral bioavailability via SNAC erodible tablets vs 1.2% for semaglutide, a 3.5-fold improvement.

Why it matters

Oral peptide delivery could eliminate the need for injections of GLP-1 medications. This study shows that combining improved peptide stability with optimized tablet formulation can dramatically improve oral absorption — potentially leading to more effective oral obesity and diabetes pills.

The numbers in context

Two permeation enhancers tested (C10 and SNAC); erodible tablet formulation; tested in monkeys for gastric delivery of a GIP/GLP-1 peptide.

How the study worked

Development and in vivo evaluation of C10 and SNAC erodible tablets in cynomolgus monkeys, with tissue distribution studies, release kinetics optimization, and comparison to oral semaglutide bioavailability.

Who was studied

Non-human primates (monkeys)

What this study cannot tell us

Monkey data may not directly predict human bioavailability; absolute bioavailability still low (<6%); single-dose study without chronic dosing; only one peptide compared to semaglutide; gastric variability (pH, motility) not fully explored; LY peptide not yet clinically available.

How to read the evidence

Preliminary preclinical evidence from a well-designed monkey study with mechanistic tissue analysis. Promising but human translation needed.

When this study was published

Published in 2024, representing advances toward next-generation oral peptide medications.

The bigger picture

Oral semaglutide (Rybelsus) was a breakthrough but absorbs poorly (1-2%). This work shows next-generation peptides designed for oral delivery could achieve much higher absorption, potentially enabling lower doses with better efficacy for obesity and diabetes treatment.

Questions still open

Can the 4.2% bioavailability be further improved with next-generation formulations?
How does the LY peptide's efficacy compare to injectable GLP-1 agonists at achievable oral doses?
Will these formulation principles translate to improved oral bioavailability in humans?

Common questions

Could this make GLP-1 pills work better than current oral semaglutide?

Yes — by designing a peptide that resists stomach acid breakdown better than semaglutide and optimizing the tablet formulation, researchers achieved 3.5 times better absorption in monkeys. This could lead to more effective oral obesity and diabetes medications.

How does the oral pill get a peptide through the stomach lining?

The tablets contain a substance called SNAC that helps in two ways: it loosens the junctions between stomach cells (letting the peptide pass between them) and it helps cells absorb the peptide directly through their membranes.

Read the original research

Development and evaluation of C10 and SNAC erodible tablets for gastric delivery of a GIP/GLP1 peptide in monkeys.

International journal of pharmaceutics, 650, 123680

View on PubMed ↗Publisher’s paper ↗

Citation

Tran, Huyen; Dogra, Mridula; Huang, Siyuan; Aihara, Eitaro; ElSayed, Mohamed; Aburub, Aktham. (2024). Development and evaluation of C10 and SNAC erodible tablets for gastric delivery of a GIP/GLP1 peptide in monkeys.. International journal of pharmaceutics, 650, 123680. https://doi.org/10.1016/j.ijpharm.2023.123680