Weekly long-acting smart insulin created by researchers

Diabetic mice, minipigs achieve week-long normoglycemia with subcutaneous smart insulin.

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Researchers at Zhejiang University created a smart insulin that releases slowly in response to blood sugar. With just one shot under the skin, it forms a small depot that works for over a week, reducing the risk of low blood sugar. This discovery could lead to a future where a single insulin injection lasts a week or more, effectively managing blood sugar levels. The study, conducted by Professor GU Zhen, was published in Nature Biomedical Engineering.

Insulin, a hormone from the pancreas, manages blood sugar, stores glycogen, and aids fat synthesis. For many with diabetes, insulin injections are crucial. However, frequent subcutaneous injections are burdensome and can lead to safety risks like hypoglycemia. This new formulation mimics the pancreas’s beta cells, sensing real-time blood sugar changes. It releases insulin slowly under normal conditions and quickly during high blood sugar, helping maintain stable glucose levels without frequent injections.

Professor GU Zhen said, “The formulation is a white powdery complex consisting of polymers with glucose-responsive molecules (fluorobenzoborate-modified poly-ʟ-lysine) and gluconic acid-modified recombinant human insulin. Current studies in the minipig model indicate that this new formulation has long-lasting and glucose-responsive insulin release properties. It could maintain normal blood sugar levels in 30 kg type 1 diabetic minipig model for over one week with a single dose, without symptoms of hypoglycemia.”

When injected under the skin, a groundbreaking insulin complex creates a reservoir for long-term storage and quick release when blood sugar rises. Professor John Buse from the University of North Carolina School of Medicine called it an exciting breakthrough. Unlike other drug formulations, this complex avoids the risk of fibrous capsule formation, ensuring efficient insulin release without hindrance. The reservoir, about the size of a pea, gradually releases insulin while the polymer material gets absorbed.

WANG Jinqiang, Ph.D., an assistant professor at Zhejiang University, mentioned that their developed materials and dosage form have a unique feature: they can prevent the formation of fibrous capsules. The team aims to evaluate the long-term compatibility of this formulation before moving on to clinical trials.

Journal reference:

  1. Zhang, J., Wei, X., Liu, W. et al. Week-long norm glycaemia in diabetic mice and minipigs via a subcutaneous dose of a glucose-responsive insulin complex. Nature Biomedical Engineering. DOI: 10.1038/s41551-023-01138-7.

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