A team of researchers from the University of Sydney and Sydney Local Health District has created an oral insulin formulation using nanotechnology. If successful in future use, the innovation could offer millions of people living with diabetes a needle-free alternative to insulin injections, potentially benefiting the estimated 75 million individuals worldwide who depend on insulin therapy. This technology would also allow the insulin to be embedded in a delivery vehicle such as sugar-free chocolate.
Dr. Nicholas Hunt, lead author from the University of Sydney’s School of Medical Sciences, and colleagues, including Professor Peter McCourt of UiT Norway’s Arctic University, developed a new method of delivering insulin via nano-carriers, which has been successfully tested on nematodes, mice, rats, and baboons at the National Baboon Colony in Australia. What sets this approach apart isn’t just the format. The insulin only releases when the body actually needs it.
Animal studies showed that the nano-scale material reacts to the body’s blood sugar levels. The coating dissolves and releases insulin when blood sugar is high, and stays intact when blood sugar is low. That glucose-responsive mechanism addresses a core limitation of conventional insulin therapy that has persisted for decades.
Why Injections Fail So Many People
According to the International Diabetes Federation, 589 million adults worldwide are living with diabetes, representing 11.1% of the adult population aged 20 to 79. That number is growing every year. More than 150 million people worldwide, including about 8.4 million Americans, rely on insulin treatment. For many of them, the act of injecting comes with consequences that go well beyond the discomfort of a needle.
A 2025 study published in Pharmaceutics noted that subcutaneous insulin administration, injecting insulin under the skin, is associated with discomfort, poor adherence, and poor distribution of insulin in the body. When insulin is injected into the fat layer under the skin rather than delivered through the liver, it spreads throughout the body in a way that doesn’t mirror how the pancreas naturally releases it.
The potential side effects can be significant as well. According to Drugs.com, hypoglycemia, dangerously low blood sugar, is the most common and serious side effect of insulin therapy, occurring in approximately 16% of type 1 and 10% of type 2 diabetic patients. Severe cases can result in seizures, coma, or cardiac events. Weight gain also remains a common side effect of insulin therapy. A systematic review and meta-analysis of 46 clinical trials found that people with type 2 diabetes gained an average of 4.3 kg during the first year of intensive insulin treatment, although the amount varied depending on the insulin regimen and treatment intensity. Basal insulin was generally associated with less weight gain than more intensive regimens.
Those side effects aren’t trivial inconveniences. They directly undermine the reason people take insulin in the first place. A 2025 study found that only around 55% of patients maintain consistent adherence to insulin therapy globally, with even lower rates in low-resource settings. Pain, fear of hypoglycemia, and undesirable weight changes are among the main reasons people skip doses or abandon treatment altogether.
The Science Behind This Diabetes Treatment: An Alternative to Insulin Injections
Researchers published their findings in Nature Nanotechnology, reporting on insulin-conjugated silver sulfide quantum dots coated with a chitosan/glucose polymer to produce a responsive oral insulin nanoformulation. Each particle is a microscopic container that holds insulin, has an intelligent coating that reads blood sugar levels, and only opens when glucose is too high. The nano-scale material is 1/10,000th the width of a human hair.
The formulation is pH-responsive, meaning it remains insoluble in acidic stomach environments but becomes active at neutral pH, making it sensitive to glucosidase enzymes, the biological triggers that cause insulin release. It distributes to the liver in mice and rats after oral administration, promoting a dose-dependent reduction in blood glucose without causing hypoglycemia or weight gain in diabetic rodents.
The liver targeting is the key innovation. When the pancreas releases insulin naturally, it goes directly to the liver via the portal vein before circulating to the rest of the body. Contrary to current injectable insulin formulations, endogenous insulin has direct access to the portal vein, regulating glucose metabolism in the liver with minimal hypoglycemia. Standard injections bypass that pathway entirely, flooding peripheral tissues first and causing blood sugar to drop faster than the body expects. This oral formulation restores the natural route.
As Professor Peter McCourt of UiT Norway’s Arctic University explained in the research announcement, injected insulin spreads throughout the body where it can cause unwanted side effects, whereas oral delivery targets the areas that need it most.
Making the formulation palatable wasn’t an afterthought. To make the oral insulin palatable, the research team incorporated it into sugar-free chocolate, an approach that was well received by animal subjects. The baboon tests, conducted at Australia’s National Baboon Colony, used this chocolate delivery format. The baboons used in initial testing were healthy, non-diabetic animals, while mice and rats with actual diabetes showed no hypoglycemia, weight gain, or fat accumulation in the liver.
Fat in chocolate actively protects the nanoparticles during digestion, giving them a better chance of surviving the acidic stomach environment and reaching the intestine intact. The sugar-free formulation means diabetic patients can consume it without affecting their glucose management before the insulin even begins to work.
Preclinical testing across animal models found that, following ingestion, the nano insulin was able to control blood glucose levels without hypoglycemia, weight gain, or any detected toxicity.
From Lab to Human Trials
Dr. Nicholas Hunt, lead author from the University of Sydney’s School of Medical Sciences, has acknowledged that a huge challenge facing oral insulin development has always been the low percentage of insulin that reaches the bloodstream when given orally. This formulation was specifically engineered to solve that absorption problem.
Endo Axiom Pty Ltd was founded by Professor Victoria Cogger, Professor David Le Couteur AO, and Dr. Nicholas Hunt after 20 years of research. Endo Axiom secured $2.2 million in backing from Australian biotech incubator Proto Axiom to help bring the novel drug delivery technology to the clinic.
Endo Axiom has secured additional investment to support the next phase, including $1,079,424 from MTPConnect’s competitive Targeted Translation Research Accelerator program in 2025, along with $500,000 from the University of Sydney Pre-Seed Fund.
Human trials are slated to be led by Endo Axiom beginning in 2025. The Phase I trial will specifically investigate the safety of the oral insulin and look at the incidence of hypoglycemia in healthy and type 1 diabetic patients. In the Phase 1a trial, participants will be given the oral insulin capsule and have their blood glucose checked 15 minutes later. They’ll then take a glucose solution so investigators can observe how quickly the oral insulin clears the added glucose out of their body.
The next step after Phase 1a will be a Phase 1b trial in people with type 1 diabetes to assess the safety and tolerability of multiple daily doses of smart oral insulin, and to provide preliminary data on whether it improves glucose control and reduces the frequency and severity of hypoglycemic events.
The researchers aim to have the oral insulin on the market by 2030.
For people currently managing type 2 diabetes, which accounts for more than 90% of diabetes cases in adults in the U.S., the news is potentially significant, though the animal studies focused primarily on type 1 diabetic rodent models. The Phase 1b trial will generate the first human data on type 1 populations, with broader type 2 applications to follow in later trial phases.
What This Means for the Diabetes Treatment Landscape
The scale of the problem this research is trying to solve is enormous. According to Grand View Research, the global insulin market was valued at USD 19.32 billion in 2024 and is projected to reach USD 23.21 billion by 2030. A diabetes treatment alternative to insulin injections that is both safer and more convenient would reshape that market and reshape the daily lives of tens of millions of people who currently structure their entire day around injection schedules.
Dr. Hunt has noted that “oral insulin has been a dream for the last 60 years for a lot of people and is still actively being pursued.” What distinguishes this formulation from previous attempts is the glucose-responsive release mechanism. Earlier oral insulin efforts failed partly because they couldn’t reliably get insulin across the gastrointestinal tract intact, and partly because they had no way of controlling when insulin released once it arrived. The quantum dot nano-carrier system addresses both problems simultaneously.
Read More: An Oral Insulin Capsule Passed Second Stage Testing
What to Do Now
Phase I human trials test safety, not effectiveness. Results establishing how well the oral insulin controls glucose in type 1 diabetic patients are likely still years away. For anyone currently managing diabetes with injections, the practical implication for now is to stay informed rather than change your treatment.
Ask your endocrinologist or diabetes care team about the trial pipeline, particularly if you or someone you care for has type 1 diabetes and struggles with injection adherence or recurrent hypoglycemia. The Phase I trial will specifically look at hypoglycemia incidence in healthy subjects and type 1 diabetic patients. If the team can reproduce the absence of hypoglycemic events observed in baboons, Dr. Hunt has said this would represent “a huge step forward.”
Two decades of research, multi-institutional funding, and clean animal data across three species place this formulation well ahead of most preliminary lab findings. Whether the human data holds up is the next question, and 2026 should bring the first answers.
Disclaimer: This information is not intended to be a substitute for professional medical advice, diagnosis, or treatment and is for information only. Always seek the advice of your physician or another qualified health provider with any questions about your medical condition and/or current medication. Do not disregard professional medical advice or delay seeking advice or treatment because of something you have read here.
AI Disclaimer: This article was created with the assistance of AI tools and reviewed by a human editor.
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