The Game Changer: Treating type 1 diabetes with glucose-responsive insulins

By Thania Benios

Since its discovery in 1921, insulin has been called one of the few miracle drugs, having saved countless lives from an otherwise incurable disease. Yet 90 years later, treating and managing type 1 diabetes (T1D) is still a tricky business.

Insulin, a hormone, is crucial to life. Without it, glucose cannot move from the bloodstream into the cells of the body to provide them with the energy they need to function. In T1D, which is an autoimmune disease, the immune system mistakenly attacks and destroys the beta cells in the pancreas that produce insulin. This immune attack leaves the body without the insulin that is needed to control blood sugar levels. As a result, the burden of managing blood sugar rests squarely on the shoulders of people with T1D, who must take multiple injections of insulin daily or infuse insulin through a pump.

But mimicking nature is a very time-consuming and difficult process. Exercise, meals and snacks—things that we all incorporate into daily life—require more than just a thought for people with T1D. Every decision means a recalibration of how much insulin to inject or infuse throughout the day, and when to inject it. And a miscalculation due to human error or guesswork can have dire and immediate consequences.

“Despite this round-the-clock vigilance, people with the disease still spend up to 70 percent of their day outside the normal blood sugar range,” says Aaron Kowalski, Ph.D., vice president of glucose control at JDRF. “So despite the effectiveness of current insulin treatments, they do not always prevent hypo- or hyperglycemic episodes, which in the short term can be very dangerous (hypoglycemia) and in the long term (hyperglycemia) cause the terrible complications of diabetes.”

The bottom line: type 1 diabetes is a difficult disease to manage.

In an effort to lift the overwhelming burden of living with T1D, JDRF is putting its resources, expertise, and academic and industry connections behind the development of a glucose-responsive insulin, a “designer” drug that could transform the lives of people with T1D, and any of those with type 2 diabetes who are insulin-dependent.

Unlike current insulin therapies, glucose-responsive insulins would act just like a surrogate pancreas, delivering insulin to the body’s tissues and organs precisely when and where it’s needed, in precisely the right amounts. The drug would only need to be taken once a day or less frequently, and wouldn’t have to be calibrated with carbohydrates, exercise, and blood glucose testing.

And since glucose-responsive insulins would be device-free—limiting finger sticks, replacing pumps, and reducing human intervention—it would drastically reduce the daily burden and cost of managing the disease (along with decreasing the risk of complications).

“Glucose-responsive insulins will be game-changers,” says Sanjoy Dutta, Ph.D., senior director of treatment therapies at JDRF. “When successful, they wouldn’t just be another incremental improvement in insulin therapy. They will provide a new way of life for people with the disease.”

The premise is simple enough: build a drug that can release insulin in the body, but designed to do so only when and where it is needed, and at exactly the right dose. Because they would be more complex than the average drug, these insulins wouldn’t release all their insulin at once, but instead would hold on to their stores until the next influx of sugar from a meal or snack. By minutely adjusting its output to the body’s needs, a glucose-responsive insulin would greatly reduce the human guesswork and human error that are inherently part of current insulin treatments.