People with diabetes may soon have a convenient new way to take insulin, thanks to groundbreaking research. Scientists are developing ways to take insulin orally or sublingually (under the tongue) as an alternative to injections, pumps, and inhalers.
A Canadian team has produced insulin drops that are placed under the tongue to be absorbed into the body. Meanwhile, a team in Australia has created “nano-carriers” for insulin that can be put into capsules or chocolates.
An Israeli company, Oramed, has been developing an oral insulin therapy since 2013, but has not yet completed clinical trials.
A new solution to a worldwide health problem
Insulin is a natural hormone, produced in the pancreas, that helps people turn food into energy. It also manages their blood sugar levels. Diabetes is a chronic disease that occurs when the body doesn’t produce enough insulin or can’t use it properly, causing blood sugar levels to rise. Untreated diabetes is a major cause of blindness, kidney failure, heart attacks, stroke, and lower limb amputation.
The World Health Organization reported 422 million people had diabetes in 2014, up from 108 million in 1980. Prevalence has been growing more rapidly in low- and middle-income countries than in high-income countries. In 2014, 8.5% of adults aged 18 years and older had diabetes. At least 150–200 million people worldwide rely on insulin therapy for their health.
Injectable insulin is currently the standard of care for diabetes because it is fast and effective. However, people with Type 1 diabetes must take insulin every day, often several times. This burden can reduce their “medication adherence” – in other words, they don’t take the needed doses on time. Furthermore, using needles to deliver medication means risking cross-contamination, needle pricks, accidental infections, and unsafe disposal of contaminated needles.
Currently, insulin doesn’t come in pill form because the digestive system would break the pill down before it could work. That’s the obstacle that the Canadian and Australian projects are working to overcome. Providing patients with a way to take insulin by mouth as an alternative to injections could have big benefits.
Sublingual insulin drops with a cell-penetrating peptide
Researchers at the University of British Columbia have developed insulin drops that are placed under the tongue. This delivery method makes it easier and more convenient for diabetes patients to manage their blood sugar levels.
The drops work thanks to a special cell-penetrating peptide, developed by Professor Shyh-Dar Li and his team. The peptide, sourced from fish byproducts, opens a pathway for insulin to pass through the lining of the mouth and into the bloodstream. Normally, insulin is destroyed in the stomach or struggles to enter the bloodstream because it’s a large molecule. But with this peptide, insulin can quickly and effectively reach the blood.
Cell-penetrating peptides are becoming a powerful and flexible tool to help proteins and other molecules move through different protective barriers in the body. These special peptides work by creating pores on the surfaces of cells, allowing proteins to enter more easily.
In preclinical tests in mice, drops developed by Dr. Li’s lab have proved to be just as effective as traditional insulin injections, without the pain or complications of needles, and without evidence of toxicity. This breakthrough could make managing diabetes simpler and more comfortable for millions of patients.
“Think of it as a guide that helps insulin navigate through a maze to reach the bloodstream quickly,” Jiamin Wu, a postdoctoral researcher in the Li Lab, told Global News. “This guide finds the best routes, making it easier for insulin to get where it needs to go.”
Two versions of the peptide are described in recent articles in the Journal of Controlled Release (here and here).
Oral insulin delivered via nano-carriers
Scientists at the University of Sydney have developed a method of taking insulin in a capsule or even inside a piece of chocolate. The insulin is enclosed in tiny nano-carriers, which are 1/10,000th the width of a human hair. The nano-carriers are so small they can’t be seen under a regular microscope.
These nano-carriers help deliver insulin directly to the liver, where it is needed most, and release it only when blood sugar levels are high. This targeted delivery reduces the risk of side effects, such as low blood sugar (hypoglycemia), which can happen with traditional insulin injections.
The new method mimics how the body naturally uses insulin, leading to better blood sugar control and fewer complications. The insulin doesn’t need refrigeration, and taking it is much easier and more discreet than injections.
“In order to make the oral insulin palatable we incorporated it into sugar-free chocolate,” said Nicholas J. Hunt at the University of Sydney who leads the project with Victoria Cogger. “This approach was well received.”
The method has been successfully tested on mice, rats, and baboons, and has shown promising results. The mice and rats did not have low blood sugar (hypoglycemia), which is a potentially dangerous side effect that can happen with traditional insulin injections. Human trials are set to begin in 2025, with hopes that this new form of insulin will be available to everyone within 2-3 years.
Read about the research in Nature Nanotechnology here.
See other human health information from the Parsemus Foundation here.
