Insulin pills may soon replace daily injections
- Date:
- March 24, 2026
- Source:
- Kumamoto University
- Summary:
- For over a century, scientists have chased the dream of insulin pills, but the digestive system kept destroying the drug before it could workâforcing millions of patients to rely on daily injections. Now, researchers at Kumamoto University have developed a clever workaround using a tiny peptide that helps insulin slip through the intestinal wall.
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For more than 100 years, scientists have pursued the idea of insulin in pill form, often described as a “dream” treatment for diabetes. The challenge has been the body itself. Enzymes in the digestive system break down insulin before it can work, and the intestine lacks a natural way to absorb it into the bloodstream. As a result, many patients still depend on daily injections, which can take a toll on their quality of life.
A team at Kumamoto University, led by Associate Professor Shingo Ito, has now developed a promising solution. Their approach uses a cyclic peptide that can pass through the small intestine, known as the DNP peptide. This platform allows insulin to be delivered orally in a way that was not previously possible.
Two Effective Strategies for Intestinal Absorption
To make this work, the researchers designed two different methods to help insulin cross the intestinal barrier:
- Mixing method (interaction-based): The team combined a modified “D-DNP-V peptide” with zinc-stabilized insulin hexamers. When given orally to several diabetes models, including chemically induced (STZ mice) and genetic (Kuma mice) models, this mixture quickly brought blood sugar levels down to normal. Stable glucose control was maintained with once-daily dosing for three consecutive days.
- Conjugation method (covalent-based): Using click chemistry, the researchers attached the DNP peptide directly to insulin, creating a “DNP-insulin conjugate.” This version lowered blood sugar just as effectively as the mixing method, confirming that the peptide actively helps transport insulin through the intestine.
Lower Doses Make Oral Insulin More Practical
One of the biggest obstacles for oral insulin has been the need for extremely high doses, sometimes more than ten times higher than injections. This new platform significantly reduces that requirement. It achieved a pharmacological bioavailability of about 33-41% compared to subcutaneous injection. That level of efficiency suggests oral insulin could become far more practical for real-world use.
Future Potential for Diabetes Treatment
“Insulin injections remain a daily burden for many patients,” said Associate Professor Shingo Ito. “Our peptide-based platform offers a new route to deliver insulin orally and may be applicable to long-acting insulin formulations and other injectable biologics.”
The findings were published in the journal Molecular Pharmaceutics. The researchers are now moving forward with additional studies, including testing in larger animal models and systems that replicate the human intestine, as they work toward eventual clinical applications.
Story Source:
Materials provided by Kumamoto University. Note: Content may be edited for style and length.
Journal Reference:
- Shoma Chikamatsu, Kosei Sakaguchi, Masataka Michigami, Kimi Araki, Shoen Kume, Midori Tokuyasu, Takeshi Masuda, Ikuo Fujii, Sumio Ohtsuki, Shingo Ito. Small Intestine-Permeable Cyclic Peptide-Based Technology Enables Efficient Oral Delivery and Glycemic Efficacy of Zinc-Stabilized Insulin Hexamer and Its Analogs in Diabetic Mice. Molecular Pharmaceutics, 2025; 23 (1): 252 DOI: 10.1021/acs.molpharmaceut.5c00902
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