In this project, Professor Hagemeyer and his team at Monash University, Australia will work to bring a new insulin delivery system closer to clinical trials. They have recently demonstrated that their first generation of insulin delivery system, called ‘Small Nano Sugar’, has a fast and efficient response to changes in blood glucose levels in animals with type 1 diabetes. 

What is Small Nano Sugar?

The Small Nano Sugar system carries insulin and a glucose-sensing molecule in tiny particles called nano sugars, which are injected under the skin. Insulin is then released from these particles, only when the body needs it. The insulin-carrying nano sugar particles react to very small changes in glucose, and release insulin only when glucose levels are outside a target range, without any input from the user.  

Prof Hagemeyer said:

“I’m thrilled to receive funding from the Type 1 Diabetes Grand Challenge for our project, together with our collaborators from the University of Melbourne and RMIT University. Our innovative approach leverages biocompatible, glucose-sensitive nano sugar particles to deliver long-lasting insulin therapy, significantly improving blood glucose management and quality of life for individuals with type 1 diabetes. The funding will accelerate further research towards clinical translation and first in human trials.”

What will Prof Hagemeyer do in this project?

In this project, Prof Hagemeyer will develop a second generation of this nano sugar-insulin system, based on advanced nanotechnology. The new design is supported by the team’s results from animals with type 1 diabetes and could bring the system a step closer to clinical trials in people with type 1 diabetes.  

 The team will check the system works effectively in realtime at mealtimes and throughout the day in primates with type 1 diabetes. Testing the system in animals will also allow the researchers to explore whether it can help protect against long-term complications of diabetes. 

How will this research help people with type 1 diabetes?

The next-generation Small Nano Sugar system has the potential to reduce the number of times people with type 1 have to inject insulin, reducing some of the burden of managing the condition. The system could also prevent dangerously low blood glucose, reducing the risk and fear of hypos, as well as the burden of multiple daily injections by keeping levels in a safe range for longer.  

Chemical engineer Prof Zhiqiang Cao and his team at the Wayne State University, USA aims to develop an even smarter insulin that can precisely manage blood glucose like a healthy pancreas.  

Developing smarter insulins

Trying to keep blood glucose levels in a target range is a constant challenge and burden for people with type 1 diabetes. Scientists are working to develop ‘smart insulins’ which can detect changes in blood glucose levels and respond by releasing the right amount of insulin at the right time. 

Prof Cao said:

“It is truly an honour to be recognised by the Novel Insulins Innovation Incubator funding panel. This award supports us in advancing our concept of glucose-responsive insulin injections. Our goal is to develop a product that addresses both mealtime and basal insulin needs, alleviating the constant management burden for people living with type 1 diabetes.”

What will Prof Cao do in this project?

Prof Cao previously developed a unique glucose-responsive insulin that overcame some of the issues linked to other smart insulin designs. Some smart insulins aren’t as powerful as currently available insulins, so people with type 1 diabetes need to take higher doses to have the same effect on lowering their blood glucose levels. 

In this project, the team plan to develop a novel insulin that addresses these problems, is more sensitive to changing glucose levels, and meets the needs of people living with type 1 diabetes better. Using a confidential new method, the team will optimise their design, checking its effectiveness and safety. They hope their insights will speed up the progression of ‘smarter’ smart insulins into clinical trials with people living with type 1 diabetes. 

How will this research help people with type 1 diabetes?

Prof Cao’s smart insulin would mean people with type 1 diabetes would experience fewer hypers and hypos, helping to lower anxiety about diabetes complications. It would also relieve people of the relentless burden of managing their condition, with fewer insulin injections and less blood glucose monitoring. 

Prof Zhen Gu and his team at the Jinhua Institute of Zhejiang University in China are designing novel insulins that respond immediately to rising blood glucose levels. In this project they will test a new kind of insulin that can be used either daily or weekly. Once injected, it forms a reservoir of insulin under the skin that is released in response to increasing blood glucose levels. 

Scientists are making strides in developing novel insulins that respond more quickly to rising in blood glucose levels without the need for close glucose monitoring. These glucose-responsive insulins mimic how the insulin-making beta cells work in people without diabetes. 

A new type of insulin

Prof Gu and his team are using a type of insulin called insulin/polymer complex as the starting point to develop a new glucose-responsive insulin. Prof Gu’s team has developed a method to combine insulin and polymer molecules.

Through experiments in cells and in mice with diabetes, the researchers have shown that the insulin/polymer molecule releases insulin when exposed to glucose and lowers glucose levels in the blood. By adding a safe glucose-sensing molecule to the insulin/polymer. Prof Gu’s team aims to create a novel insulin that will maintain blood glucose levels without causing hypos.

What will Prof Gu do in this project?

Prof Gu and his team will now improve their glucose responsive insulin by ensuring that all its components work together in the most effective way by fine-tuning the amounts of each of them. They’ll then test the glucose-responsive insulin to make sure it releases insulin correctly from the reservoir, especially when blood glucose levels are high. The team will also investigate how well the novel insulin can control glucose levels in cells and in animals with diabetes. 

By the end of the project, the researchers aim to have developed a high-quality glucose-responsive insulin that can be mass-produced in a cost-effective way. This will bring this novel insulin a step closer to clinical trials in people with type 1 diabetes. 

How will this research help people with type 1 diabetes?

The goal of this research is to create a novel insulin that effectively regulates blood glucose levels without causing them to drop too low. By speeding up insulin release from the reservoir after eating and slowing down when blood glucose falls below a safe point, this novel insulin could help people with type 1 diabetes to have steadier blood glucose levels, and lower anxiety around hypos. 

The researchers will also design the new insulin to be used less frequently than current insulins, reducing the time people with type 1 have to spend managing their condition. 

Prof Zhen Gu said:

“The clinical translation of this long-acting smart insulin will significantly enhance health and quality of life of people with type 1 diabetes.” He hopes that this type of insulin will one day be able to reduce the need for multiple daily insulin injections and limit the highs and lows in blood glucose that people living with type 1 diabetes experience.”

Professor Webber, a biomedical engineer at the University of Notre Dame, USA, designs medicines to mimic natural molecules in the body. Prof Webber and his team developed a ‘smart insulin’ comprising an injectable glucose-responsive reservoir.  

Designing insulin nanocomplexes

Professor Webber’s team has developed a smart insulin delivery system that uses tiny particles called nanocomplexes, which contain insulin. These nanocomplexes can be injected under the skin to create a reservoir of insulin. If glucose levels in the blood rise, insulin is automatically released from the stored particles into the bloodstream. 

This allows blood glucose levels to be managed in realtime, as less insulin is released when blood sugar levels are low. The team has shown that in pigs with type 1 diabetes, a single injection of the insulin nanocomplexes is enough to keep glucose levels stable for a whole week. 

What will Prof Webber do in this project?

In this project, Prof Webber and his team will continue to develop this smart insulin delivery system and test the function in pigs exposed to relevant real-life scenarios. They will explore more reliable ways to manufacture the insulin-containing nanocomplexes to allow them to be stored at room temperature.  

By collaborating with a non-profit company dedicated to developing of new treatments and cures, the team will also attempt to reduce the amount of the smart insulin needed in one daily injection to achieve the same blood glucose management. They will consider risk of hypos in response to exercise, eating vs not eating, and illness by testing it in pigs with diabetes. 

The research will help the team find out how quickly different doses of the new smart insulin bring down blood glucose levels at different times during the day, including at mealtimes, during exercise and when not eating.  

How will this research help people with type 1 diabetes?

This research project will bring smart insulins a step closer to clinical trials in people with type 1 diabetes. The smart insulin nanocomplex Prof Webber’s team is developing could one day help people with type 1 manage their blood glucose levels with fewer injections and a reduced risk of hypos. This would help people with type 1 to think less about their diabetes and more about living life to the full.  

Prof Matthew Webber said:

“Our work will develop and test new insulin formulations that offer simplified dosing schedules and which adjust their potency according to real-time blood glucose levels. Such technology will allow for a more autonomous therapeutic approach to treat type 1 diabetes, affording accurate blood glucose control while minimising side-effects.”

Prof Michael Weiss and his team at Indiana University, USA will develop and test a novel protein molecule that combines insulin and glucagon to help reduce the burden of blood glucose highs and lows for people living with type 1 diabetes.  

Glucagon and insulin

Unlike insulin, which helps remove glucose from the blood, glucagon is a hormone that stimulates the liver to release more glucose when levels in the blood run low. Prof Weiss and his team have designed and run initial tests on a molecule that combines insulin and glucagon.  

 By combining both hormones, the researchers hope their combined hormone can help prevent highs and lows in blood glucose and improve quality of life for people living with type 1 diabetes. They’ve tested the molecule in rats with type 1 diabetes and found that it can lower risk of hypos both at mealtimes and throughout the day.

What will Prof Weiss do in this project?

In this project Prof Weiss and his team will improve the design of the glucagon-insulin molecule to optimise time-in-range. They’ll run experiments in rats with type 1 diabetes to test how stable the dual hormone molecule is and confirm that it prevents both hypers and hypos.  

 They will also explore different ways to manufacture this insulin-glucagon molecule, to find the cheapest and easiest way to make large quantities, so it can be tested in human clinical trials in the future.  

Prof Weiss said:

“My colleague Prof Raimund Herzog at Yale and our team at Indiana University are most grateful to the Type 1 Diabetes Grand Challenge programme for supporting our efforts to prevent hypoglycemia in type 1 diabetes through the development of ‘smart’ insulin-glucagon fusion proteins. Thanks to Grand Challenge funding, we have the opportunity to test our ideas to enhance the quality of life for individuals with type 1 diabetes to make managing type 1 easier and safer to accomplish.”

How will this research help people with type 1 diabetes?

People with type 1 diabetes are constantly aware of the risk of hypos. Unlike other novel insulins, the aim of this research project is to protect against hypos by activating glucagon if blood glucose levels fall too low. 

 This research could pave the way to reducing highs and lows in blood glucose without the need for constant monitoring. It could be particularly helpful for people who often have hypos or don’t feel the symptoms of hypos (known as hypo unawareness). 

Prof Chou is a diabetes expert at Stanford University, USA who develops proteins to treat type 1 diabetes and other conditions. In this project, Professor Chou and his team will develop and test an ultrafast-acting insulin that’s only active when needed and could reduce the risk of blood glucose highs and lows in people with type 1 diabetes. 

Fast-acting insulins

Synthetic, fast-acting insulins have been developed that make it easier for people with type 1 diabetes to manage their blood glucose levels. Despite these advances, there’s still a delay between injecting insulin and the point it starts to bring down blood glucose levels.  

This delay is in part because current fast-acting insulins are hexamers (group of six molecules) which need to get separated from each other to form single insulin molecules. Even once separated, the single molecules still tend to cluster together in pairs, making it more difficult for them to do their job. 

What will Prof Chou do in this project?

Prof Chou and his team want to overcome the problem by designing an insulin molecule that doesn’t cluster, so it can get into the bloodstream even more quickly. The team’s design is based on insulin molecules found in a surprising place – venom from the cone snail, a type of underwater snail that uses insulin as a weapon. 

The novel insulin will be designed to mimic natural insulin produced in the pancreas in people without diabetes. This means that, compared to currently available insulins, this novel insulin will be released more quickly when blood glucose increases. When blood glucose levels fall, the insulin will also stop acting sooner, reducing the risk of hypos.  

Prof Chou said:

“Our proposed research project focuses on developing ultrafast acting insulin, which aims to significantly improve the quality of life for individuals living with type 1 diabetes. By providing faster and more precise glucose control, our work promises to enhance daily management, ultimately leading to healthier and more fulfilling lives for people with type 1.”

How will this research help people with type 1 diabetes?

The delay between an insulin injection and when it acts on glucose in the blood can mean people experience long blood glucose highs, particularly at mealtimes when blood glucose levels can increase quickly. Ultrafast insulins could help address this delay and reduce the risk of the diabetes complications linked to high blood glucose levels over a long time. The shorter duration of action would reduce the risk of insulin-induced hypos. These two improvements would enhance the quality of life for people with type 1 diabetes. 

Chemistry catching up with technology

We also need faster acting insulins, like Prof Chou’s, to fully close the loop in technology that links continuous glucose monitors with insulin pumps (known as closed-loop insulin delivery systems). Creating a faster insulin that also stops working sooner will enable better integration with closed-loop insulin delivery systems. Prof Chou’s ultrafast insulin would bring this technology closer to the normal functioning of a healthy pancreas as it would remove the need for the individuals to tell the system when they are about to exercise or eat.