A new study, published in Nature, has demonstrated that in animal models, a newly developed form of insulin can switch on and off in response to changing blood glucose levels, effectively lowering high glucose levels without causing dangerous hypos.
The new insulin, named NNC2215 was developed by an international team involving companies based in Denmark, the UK, and the Czech Republic as well as the University of Bristol. It features a sophisticated molecular ‘switch’ mechanism made of two parts: a ring-shaped structure and a molecule with a similar shape to glucose called a glucoside. When blood sugar levels are low, the glucoside binds to the ring, keeping the insulin in an inactive, or ‘off’ state to prevent further lowering of blood sugar. As blood glucose rises, the glucoside is replaced by glucose itself, triggering the insulin to shift its shape and become active, helping bring blood sugar levels down to safer ranges.
‘Smart’ insulins such as this one have the potential to be truly transformative in the management of type 1 diabetes. Unlike traditional insulin, which needs to be carefully dosed to avoid hypoglycemia, a ‘smart insulin’ would only activate when needed, making it a safer and more efficient treatment.
New types of insulin like NNC2215 could lead to a significant improvement in quality of life for people living with type 1 diabetes, helping to reduce the constant burden of managing blood sugar levels.
Researchers who developed NNC2215 found it to be as effective as human insulin at lowering blood glucose in rats and pigs. No timeline has been given for the next steps in developing this product or for clinical trials in people with diabetes, but this is a significant step forward in the search for more advanced and reliable treatments for diabetes. This proof of concept highlights how clever chemistry could unlock entirely new options for people with type 1 diabetes.
Dr Tim Heise, Vice Chair of our novel insulins Scientific Advisory Panel, said:
“This elegant study shows that it is feasible to quickly switch insulin action on and off depending on prevailing glucose levels, and to minimise the risk of hypoglycaemia in pigs.
“While this study certainly is important progress, many more steps will have to follow to establish glucose-sensitive insulins as treatment for people with diabetes. Nevertheless, I am confident that the intense research in glucose-sensitive insulins including the developments funded by the Type 1 Diabetes Grand Challenge programme will manage to achieve this goal.”
Rachel Connor, Director of Research Partnerships at Breakthrough T1D in the UK, said:
“It’s exciting to see data on a new form of insulin that can change its structure to switch activity on and off as glucose levels change. This shows us that a future where people with diabetes no longer need to worry about hypos as a result of insulin therapy could be within reach.”
Dr Elizabeth Robertson, Director of Research at Diabetes UK, said:
“This research represents a significant step forward in the global effort to develop the next generation of “smart” insulins. The hope is that these will ease the constant challenge of managing blood sugar highs and lows, and improve the physical and mental health of millions of people worldwide with diabetes who rely on insulin therapy. We’re excited to part of this endeavour through our Type 1 Diabetes Grand Challenge programme.”
The Type 1 Diabetes Grand Challenge is currently funding six research projects aimed at developing new types of insulin. The goal of the research programme is to eventually offer a range of personalised treatment options for people with type 1 diabetes, tailoring therapies to meet each patient’s unique needs. This exciting progress in insulin innovation brings us one step closer to that vision.