Researchers at Kumamoto University have developed a peptide-based technology platform that may allow insulin to be taken orally, potentially replacing daily injections for millions of diabetes patients. The findings were published in Molecular Pharmaceutics.

For over a century, scientists have pursued oral insulin delivery, but the digestive system breaks down the hormone before it can reach the bloodstream, and the intestine lacks a natural absorption mechanism. The new approach uses a cyclic peptide called DNP that can pass through the small intestine, enabling oral insulin delivery.

The research team, led by Associate Professor Shingo Ito, tested two methods. The first involved mixing a modified D-DNP-V peptide with zinc-stabilised insulin hexamers. When administered orally to diabetic mouse models, this mixture rapidly normalised blood glucose levels, with stable control maintained through once-daily dosing over three consecutive days. The second method used click chemistry to attach the DNP peptide directly to insulin, creating a conjugate that proved equally effective.

A significant barrier to oral insulin has been the requirement for extremely high doses compared to injections. The new platform achieved pharmacological bioavailability of approximately 33–41% relative to subcutaneous injection, substantially reducing the dose needed and making oral administration more practical.

The researchers noted that their peptide-based platform may also be applicable to long-acting insulin formulations and other injectable biological therapies. Additional studies are planned, including testing in larger animal models and systems that replicate the human intestine, as the team works towards clinical applications.

Source: Science Daily / Kumamoto University (Molecular Pharmaceutics, 2026)