There are approximately 425 million people worldwide with diabetes. About 75 million of them inject insulin daily. Now they may soon have a new alternative to syringes or insulin pumps. Scientists have found a new way to supply the body with smart insulin.
The new insulin can be consumed by taking a capsule or even better, inside a piece of chocolate.
Inside these we find tiny nanocarriers in which insulin is encapsulated. The particles are 1/10,000th the width of a human hair and so small that you can’t even see them under a normal microscope.
This way of taking insulin is more precise because it delivers insulin quickly to the areas of the body that need it most. When you take insulin with a syringe, it spreads throughout the body where it can cause unwanted side effects.”
Professor Peter McCourt at UiT, Norway Arctic University
He is one of the researchers behind the study. The research was recently published in Nature Nanotechnology.
It is delivered to the liver
Researchers at the University of Sydney and the Sydney Local Health District, in collaboration with UiT, discovered many years ago that it was possible to transport drugs via nanocarriers to the liver. The method was then further developed in Australia and Europe.
Many medications can be taken by mouth, but until now people had to inject insulin into the body. McCourt explains that the problem with nanocarrier insulin is that it breaks down in the stomach, so it doesn’t get to where it’s needed in the body. This has been a major challenge in developing an oral diabetes drug.
But now researchers have solved this challenge.
“We created a coating to protect 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, the liver,” says McCourt, who is a liver biologist. .
The coating is then broken down in the liver by enzymes that are only active when blood sugar levels are high, releasing insulin where it can then act on the liver, muscles and fat to remove sugar from the blood.
“This means that when blood sugar is high, there is a rapid release of insulin, and more importantly, when blood sugar is low, no insulin is released,” says Nicholas J. Hunt at the University of Sydney, who, with with Victoria Cogger, lead the project.
He explains that this is a more practical and patient-friendly method of diabetes management because it significantly reduces the risk of a low blood sugar event, i.e. hypoglycaemia, and allows controlled release of insulin according to the patient’s needs, unlike injections where all the insulin is released in one dose.
Fewer side effects
The new method works similarly to how insulin works in healthy people. The pancreas produces insulin which first passes through the liver where much of it is absorbed and keeps blood sugar levels stable. In the new insulin method, the nanocarrier releases insulin into the liver, where it can be taken up or enter the blood to circulate around the body.
“When you inject insulin under the skin with a syringe, much more goes into muscle and fat tissue than would normally happen if it were released from the pancreas, which can lead to fat storage. It can also lead to hypoglycemia, which can be dangerous for people with diabetes.
With the new method, there will be fewer such side effects.
Plus, you don’t have to stick yourself with a needle, and you can get the medicine you need in a slightly more discreet way. Also, this form of insulin does not need to be refrigerated.
Tested on baboons
Oral insulin has been tested in nematodes, mice and rats. And finally, the drug has now been tested on baboons at the National Baboon Colony in Australia.
“To make oral insulin palatable, we incorporated it into sugar-free chocolate, an approach that was well received,” says Hunt.
He says 20 baboons have taken part in this study. When they took the drug, their blood sugar dropped.
The baboons were normal, healthy baboons, but oral insulin has also been tested in mice and rats that actually have diabetes. The mice and rats did not experience low blood sugar events (hypoglycemia), weight gain, or fatty liver accumulation, overcoming current challenges with injectable and other oral insulins.
What remains now is to test the new method on humans.
Ready to use in 2-3 years
“Human trials will begin in 2025 led by spin out company Endo Axiom Pty Ltd. The clinical trials are conducted in 3 phases; in the phase I trial we will investigate the safety of oral insulin and critically examine the incidence of hypoglycemia in healthy patients and patients with type 1 diabetes. Our team is very excited to see if we can we replicate the effects of the absence of hypoglycemia seen in baboons in humans, as this would be a huge step forward. Experiments follow strict quality requirements and must be carried out in collaboration with doctors to ensure they are safe for test subjects,” says Hunt.
“After this phase I we will know that it is safe for humans and we will investigate how it can replace injections for diabetic patients in phase 2 trials,” says the researcher.
The researchers hope that the new drug may be ready for use by everyone in 2-3 years.
Source:
Journal Reference:
Hunt, NJ, et al. (2024). Oral nanotherapeutic insulin formulation with reduced hypoglycemic episodes. Nature Nanotechnology. doi.org/10.1038/s41565-023-01565-2.
