The Dream of “Smart” Insulin

Imagine this: insulin in response to changes in blood glucose. Insulin that works when you need it and turns off when you don’t.

Drugmakers have been working on what is called “smart insulin” for decades. Smart insulin can allow diabetics to more aggressively target normal blood glucose levels. It may reduce the risk of both hypoglycemia and hyperglycemia and improve health outcomes in both the short and long term.

“We want a lot chemically in developing ‘smart’ insulin,” says Matthias von Herrath, MD, director of science at the Diabetes Institute and vice president and senior medical director at Novo Nordisk.

Today, this innovation, not to mention the shelves of local pharmacies, was a breakthrough, but it was a very far from human exams. Dr. Von Herrath spoke to diabetes daily about his recent successful experiment with Novo Nordisk’s recent glucose-responsive insulin. Let’s take a closer look at the advances the researchers have made and why it is so complicated.

Smart insulin must be perfect

“Developing glucose-responsive insulin means we need to build molecules that become active when we see glucose,” says Von Herrath, who is not directly involved in Novo Nordisk’s research on smart insulin.

“I know that type 1 people think it might be a holiday,” says Von Herrath. But again, chemically, it asks a lot from the molecule. It’s not easy to construct that type of molecule and only become active when glucose is visible. ”

Von Herrath has appointed some of the most important obstacles.

Smart insulin requires extreme accuracy: Glucose-responsive insulin must be extremely accurate to ensure safety. You need to know exactly when it will be released. You also need to know when you’re going to do it Stop Release of insulin. “What happens if you eat and become active? all Just the right amount with glucose sensing insulin? Again, this is a very big question! ” says von Herat.

Smart insulin runs the risk of cross-reactivity. There are other things in the body that can look like glucose, explains von Herat. “This poses a great safety risk when these glucose sensory molecules intersect with other drugs and hormones that can be confused with glucose.” Von Herrath says this is a major concern for conducting extensive research.

Diabetes is more than just insulin: Within 20 seconds of diet, pancreatic islet cells begin to communicate with various cells in the body. This includes beta cells that produce insulin, but there are many other cells and hormones that play an important role in the way the body manages food.

Smart insulin must be perfect: Imagine a day’s worth of “smart insulin” sitting in your system waiting to be caused by an increase in glucose levels. What happens if everything suddenly becomes active for no reason? Like an insulin pump that throws 50 units of insulin into your body At once. This can easily be fatal. For glucose-sensing insulin to be truly safe for human use, it must be inherently perfect. It cannot be easily confused or confused by other aspects of the body.

New molecules

The challenges are great, but researchers have made important advances.

Scientists at Novo Nordisk have designed a molecule called NNC2215. This molecule essentially has a “switch” that responds to increased levels of glucose in the bloodstream, making insulin more or less active. When blood sugar levels rise sufficiently high, insulin becomes more active. When blood glucose levels drop, the molecule’s action slows down, closing the switch and not being picked up.

The first successful exam for NNC2215 was recently held. A team led by researcher Rita Slaaby tested the molecule’s effectiveness using rat and pig models. When blood glucose levels increased from 50 mg/dL to 360 mg/dL, glucose-responsive insulin was more responsive and occupied more glucose.

Results: New insulin has been proven to be as effective as human insulin in lowering blood glucose levels. And, as was hoped, insulin was significantly less active when exposed to hypoglycemia.

“Chemistry is progressing in amazing ways,” says Von Herrath. “I’m surprised that it’s possible! When I first grew up 20 years ago, I thought, “What a bunch of Baronies! No one can build something that works that way. It’s impossible to ski.”

Building Blocks

The NNC2215 is not yet human ready. It has also been years since its approval by the US Food and Drug Administration. However, with its success, von Herat changed his song about the possibility of glucose-responsive insulin.

“When I first saw these advancements and chemistry, I was like, ‘It’s okay, this is amazing’ but I’d be very careful to say it’s out there. It’s going on, but there’s a long way to go. ”

Von Herrath also says that this first type of glucose-responsive insulin is not a magical solution to the challenges of dietary administration, like many people with Type 1. I calm my expectations that they will become a quick-acting insulin that they can handle food,” says von Herat. “I don’t want to be disappointed by anyone, but I think it will take more time.”

The challenge, he says, challenges the serious accuracy of having to demonstrate that such drugs are reasonably safe.

“It has to work with very high specificity and sensitivity. It has to be completely fail-safe. It cannot leak, like a gas line. It has to be very accurate.”

Regardless of the long road ahead, Von Herrath says progress is important and worthy of celebration.

“At the Diabetes Institute, we celebrate every little victory. Even these glucose-sensory insulins should celebrate progress, small victory,” he adds. “But this is a road building block that requires a fair amount of small victory.”

He is optimistic and excited about the future of “smart” insulin, but von Herat knows that his perspective is not the same as those living with the daily burden of type 1 diabetes.

“I’m a glass guy, but it’s easy to say when you’re not living with your own T1D,” says Von Herrath. “But patients need to understand this study and why it is so challenging. Ten years ago, I didn’t think this was possible, so we came a long way.”