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Novel insulins

Early research shows glucose-responsive insulin tablets are safe and effective in animals

Researchers have developed a new oral insulin that travels in an inactive state to the liver and is only activated by rising blood glucose levels.
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Josie Clarkson 29 January 2024
A small container containing three tablets of a novel glucose-responsive oral insulin.

A photo of the new glucose-responsive insulin tablets the research team has developed.

Researchers from Australia and Norway have developed a new form of insulin that can be taken by mouth rather than injection. The pills travel through the digestive system to the liver, where they only release insulin when they detect high glucose levels. The international team published their research in Nature Nanotechnology in January 2024.

Nanocarriers take insulin to the liver

Insulin breaks down easily in acidic environments like our stomachs, where there is a low pH, a measure of acidity. The researchers have overcome this challenge by attaching insulin to tiny particles called nanocarriers. Too small to see with a standard microscope, nanoparticles measuring just 1/10,000th the width of a human hair carry insulin safely through the body.

Professor Peter McCourt at UiT Norway’s Arctic University, one of the researchers in the study, said: “We have created a coating to protect the insulin from being broken down by stomach acid and digestive enzymes on its way through the digestive system, keeping it safe until it reaches its destination, namely the liver.”

Glucose-responsive release

The nanocarriers can also detect a chemical that is only present when glucose levels are high. When they sense this chemical, they release the insulin they’re carrying so that it can remove the excess glucose.

Dr Nicholas Hunt at the University of Sydney, who co-leads with project with Dr Victoria Cogger, said: “This means that when blood sugar is high, there is a rapid release of insulin, and even more importantly when blood sugar is low, no insulin is released.” This means the insulin can help control blood glucose without causing unwanted hypos.

Benefits over insulin injections

There are many advantages to taking insulin via the mouth rather than injections. Professor Peter McCourt said: “This way of taking insulin is more precise because it delivers the insulin rapidly to the areas of the body that need it most. When you take insulin with a syringe, it is spread throughout the body where it can cause unwanted side effects.”

Removing the need for insulin injections could make managing type 1 easier for children and people with needlephobia. Unlike vials of liquid insulin, these insulin pills don’t need to be kept cold. This feature could make insulin more accessible for people living in hot countries or with limited electricity as well as helping making travelling with type 1 easier.

Effective in animal studies

The researchers have given their promising new insulin pills to mice and rats that have diabetes. The insulin reduced the rodents’ glucose levels without causing hypoglycaemia or weight gain. The team then tested whether their insulin could be toxic to humans by giving it with sugar-free chocolate to a group of 20 healthy adult baboons. Encouragingly, the insulin-laced chocolate lowered the baboons’ blood glucose levels without harming them.

Clinical trials coming in 2025

The research is still at an early stage and we have a lot to do before this insulin could be available for people with type 1. Clinical trials in people will start in 2025 and will initially look at the safety of the oral insulin and the incidence of hypoglycemia in people with and without type 1 diabetes.

Dr Nicholas Hunt said: “Our team is very excited to see if we can reproduce the absent hypoglycemia results seen in baboons in humans, as this would be a huge step forward.  After this phase we will know that it is safe for humans and will investigate how it can replace injections for people with type 1 diabetes.”

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