On Jan. 23. 2026, a research team at Kumamoto University, led by Associate Professor Shingo Ito, announced they have developed a breakthrough drug-delivery platform using a small-intestine-permeable cyclic peptide known as the DNP peptide, enabling efficient oral delivery of insulin.

The researchers established two effective approaches to facilitate the intestinal absorption of insulin:

Mixing method (interaction-based): A modified “D-DNP-V peptide” was simply mixed with zinc-stabilized insulin hexamers. Oral administration to multiple diabetes models—including chemically induced (STZ mice) and genetic (Kuma mice) models—rapidly reduced blood glucose levels to the normal range. Consistent glycemic control was maintained with once-daily dosing for three consecutive days.

Conjugation method (covalent-based): Using click chemistry, the DNP peptide was directly conjugated to insulin to form a “DNP–insulin conjugate.” This produced glucose-lowering effects comparable to the mixing method, confirming active peptide-mediated intestinal transport.

Unlike previous oral insulin approaches requiring very high doses (often over ten times that of an injection), this platform achieved a pharmacological bioavailability of approximately 33–41% relative to subcutaneous injection. This result demonstrates a substantial reduction in the amount of insulin needed for oral administration and marks a key step toward practical clinical use.

The team is now progressing toward translational studies, including evaluations in large animal models and human intestinal systems. The study was published in Molecular Pharmaceutics.