‘New Era’ in Insulin Possible if Research Successful

A multi-institutional partnership has funded six new research projects aimed at developing novel insulin analogs that more closely mimic the action of a healthy pancreas. 

The Type 1 Diabetes Grand Challenge comprises Diabetes UK, JDRF (now called “Breakthrough T1D” in the United States), and the Steve Morgan Foundation. It will provide a total of £50 million (about $64 million in US dollars) for type 1 diabetes research, including £15 million (~$19 million) for six separate projects on novel insulins to be conducted at universities in the United States, Australia, and China. Four will aim to develop glucose-responsive “smart” insulins, another one ultrafast-acting insulin, and the sixth a product combining insulin and glucagon. 

“Even with the currently available modern insulins, people living with type 1 diabetes put lots of effort into managing their diabetes every day to find a good balance between acceptable glycemic control on the one hand and avoiding hypoglycemia on the other. The funded six new research projects address major shortcomings in insulin therapy,” Tim Heise, MD, vice-chair of the project’s Novel Insulins Scientific Advisory Panel, said in a statement from the Steve Morgan Foundation. 

All six projects are currently in the preclinical stage, Heise told Medscape Medical News, noting that “the idea behind the funding program is to help the most promising research initiatives to reach the clinical stage.”

Glucose-responsive, or so-called “smart” insulins, are considered the holy grail because they would become active only to prevent hyperglycemia and remain dormant otherwise, thereby not causing hypoglycemia as current insulin analogs can. The idea isn’t new. In 2010, there was excitement in the type 1 diabetes community when the pharmaceutical company Merck acquired a smaller company called SmartCells that had been working on a “smart insulin” for several years. But nothing came of that. 

“The challenges then and today are pretty similar. In particular, it is quite difficult to find a glucose-sensing moiety that is safe, reacts sufficiently to relatively small changes in the human body in both falling and increasing glucose, and can be produced in large quantities,” Heise, lead scientist and co-founder of the diabetes contract research organization Profil, based in Neuss, Germany, told Medscape Medical News.

Several papers since have reported proof-of-concept in rodents, but there are no published data thus far in humans. However, in recent years the major insulin manufacturers Novo Nordisk, and Eli Lilly have acquired smaller companies with the aim of smart insulin development. 

It will still take some time, Heise said. “The challenges are well understood, although difficult to overcome. There has been quite some progress in the development of glucose-sensing moieties including, but not limited to, nanotechnological approaches.”

Applications for the newly funded projects “were thoroughly reviewed by a large panel of scientists with different areas of expertise. At the end, there was agreement in the review panel that these projects deserved further investigation, although considering their early stage, there still is a substantial risk of failure for all these projects,” he told Medscape. 

The development path might be a bit more straightforward for the other two projects. Ultra–fast-acting insulin is needed because the action of the current ones, Novo Nordisk’s Fiasp and Eli Lilly and Company’s Lyumjev, is still delayed, potentially leading to postmeal hyperglycemia if administered after or immediately prior to eating. “A truly rapid short-acting insulin might make it finally possible to progress from hybrid to fully closed loop systems, allowing a technological ‘cure’ for people with diabetes,” Heise said in the statement. 

And a protein combining insulin with glucagon could help minimize the risk for hypoglycemia, which still exists for current insulin analogs and remains “one of the major concerns associated with insulin therapy today,” he noted. 

Heise told Medscape Medical News that compared with “smart” insulin, development of the other two products “might be a bit faster if they succeed. But none of these approaches will make it to market in the next 5 years, and if one entered clinic within the next 2 years, that would be a huge success.” Nonetheless, “these research projects, if successful, might do no less than heralding a new era in insulin therapy.”

Heise is an employee of Profil, which has worked with a large number of the major diabetes industry manufacturers. 

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker.