Experimental Insulin Pill Could Reduce Need for Injections

Researchers have developed an oral form of insulin that lowers glucose levels in animal models. The oral insulin, encased in a nano-carrier that delivers insulin to the liver, is expected to begin human trials in 2025. The study is published in Nature Nanotechnology.

Overcoming a major challenge with encapsulated insulin

Of the approximately 422 million people with diabetes worldwide, around 75 million must self-inject insulin each day.

Insulin injections can be burdensome, expensive and tricky for patients; but what if these could be replaced with new “smart insulin” pills?

Researchers have developed insulin encased in tiny nano-carriers, each 1/10,000^th the width of a human hair, that may enable insulin to be administered orally instead of injected.

“This way of taking insulin is more precise because it delivers the insulin rapidly to the areas of the body that need it most,” said Peter McCourt, study co-author and a professor at the University of Tromsø (UiT) Norway’s Arctic University. “When you take insulin with a syringe, it is spread throughout the body where it can cause unwanted side effects.”

Nano-carrier may make for fewer side effects

The nano-carrier approach was developed in collaboration with the University of Sydney and the Sydney Local Health District. The researchers found it was possible to use this method to direct the delivery of medicines, in this case insulin, to the liver.

However, one of the major problems is that the capsule gets broken down in the stomach before reaching its intended destination in the body – a major stumbling block for the development of oral diabetes medications.

But McCourt and colleagues describe how they have solved this issue. “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,” McCourt explained.

The capsule’s coating is broken down only under specific conditions – when enzymes, produced only when blood sugar levels are high, are released from the liver. This releases the insulin from the capsule, allowing it to work in the liver, muscle and fat.

“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,” said Nicholas J. Hunt, the lead author of the study and a senior lecturer at the University of Sydney.

McCourt explains that insulin injections, in which the insulin is released all in one go, can lead to low blood sugar events, i.e., hypoglycemia. On the other hand, the capsules could be a more practical and patient-friendly method, allowing for more controlled insulin release.

In this way, the method works similarly to the healthy pancreas, where insulin is produced before passing through the liver for absorption and maintenance of blood sugar levels.

The method also allows for more discreet dosing and doesn’t require refrigeration, unlike insulin injections.

Human trials on the horizon

The oral insulin formulation has been tested in preclinical studies using nematodes (roundworms), mice, rats and now baboons.

In the baboon study, the insulin was prepared in sugar-free chocolate, which was well-received by the 20 baboons involved in the study from the National Baboon Colony in Australia. These animals were healthy, and the researchers observed that their glucose levels successfully dropped.

Additionally, mouse and rat models with diabetes showed that the oral insulin did not bring about hypoglycemia, weight gain or liver fat accumulation.

Now, the researchers’ goals turn towards human trials, which they hope will begin in 2025.

“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,” said Hunt. “The experiments follow strict quality requirements and must be carried out in collaboration with physicians to ensure that they are safe for the test subjects.”

“After this Phase 1 [clinical trials], we will know that it is safe for humans and will investigate how it can replace injections for diabetic patients in Phase 2 trials,” he continued.

Reference: Hunt NJ, Lockwood GP, Heffernan SJ, et al. Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycemia. Nat Nanotechnol. 2024:1-11. doi: 10.1038/s41565-023-01565-2

This article is a rework of a press release issued by UiT The Arctic University of Norway. Material has been edited for length and content.