For millions of people with diabetes, managing blood sugar is a delicate, daily dance. One wrong move — a little too much insulin or a forgotten dose — and the consequences can be dire. A team of researchers, however, has now taken a huge step toward improving the lives of diabetes patients.

They’ve created what some call a “holy grail” in diabetes care: insulin that knows when to switch itself on and off.

Imagine insulin that lies dormant in the body, springing to life only when it senses rising glucose levels. This “smart” insulin promises to reduce the constant juggling act people with diabetes endure, keeping blood sugar within a safe range while preventing the dangerous dips that can lead to seizures, unconsciousness, or even death.

The Promise of Smarter Insulin

Diabetes demands attention — constant, unrelenting attention. For people with type 1 diabetes, that means multiple insulin injections a day, often timed with precision. But even with careful planning, the body doesn’t always cooperate. Blood sugar can swing unpredictably, triggered by everything from a skipped meal to a bout of exercise.

For decades, scientists have dreamed of insulin that could take on the burden of regulating blood sugar — and, ideally, automatically. Until now, the options have been limited. Traditional insulin injections can lower glucose effectively, but once injected, there’s no turning back. And, while too little insulin can be extremely dangerous for patients with type 1 diabetes, too much insulin can drive glucose to a dangerously low state known as hypoglycemia. To prevent this, patients often take conservative doses of insulin, which may result in poor blood sugar control over the long term.

The new insulin developed by a team led by Rita Slaaby at Novo Nordisk in Denmark is remarkably different. This insulin, called NNC2215, is engineered with a molecular “switch.” When glucose levels rise, the insulin activates. When glucose levels fall, it turns off. In tests on animals, NNC2215 effectively lowered blood sugar — and without the crashes that often follow traditional insulin injections.

A Step Closer to the Holy Grail

The development of glucose-responsive insulin (GRI) has long been seen as the future of diabetes treatment. Unlike traditional insulin, which operates in a rigid and fixed way, GRI adapts to the body’s needs in real time.

By adding a glucose-binding macrocycle and glucoside to the insulin molecule, the research team created the glucose-dependent switch. In laboratory studies, the researchers observed a 3.2-fold increase in insulin activity as glucose levels rose from 3 to 20 mM. This range covers the fluctuations seen in diabetes.

Diabetic rats treated with NNC2215 demonstrated better control over blood sugar fluctuations without experiencing dangerous drops in glucose levels. In one study, glucose tolerance tests in rats showed that NNC2215 could reduce blood sugar spikes after a meal, mimicking the natural increase in insulin activity that occurs in healthy individuals. Similar findings were reported in experiments involving pigs.

“Insulin conjugates with properties such as NNC2215 hold promise for improving the treatment of diabetes by potentially lowering the risk of hypoglycaemia and partly covering the need for fast-acting insulin at mealtime. The combination of these two features should allow for more aggressive insulin titration compared to current insulin therapies to achieve normal glucose levels without increasing the risk of hypoglycaemia. This could improve both the short-term and long-term risks and complications associated with diabetes,” wrote the researchers in their study.

This new approach could fundamentally change how insulin is used. In the future, patients may only need to inject this smart insulin once a week, instead of several times a day. A lot of diabetes-related complications are because patients fail to comply with this strict regimen. But with GRI, the burden of managing blood sugar could be lifted from patients’ shoulders.

Dr. Tim Heise, a member of the Type 1 Diabetes Grand Challenge, a global effort to accelerate diabetes research, is optimistic. “Smart insulins could come as close to a cure as any drug therapy for type 1 diabetes,” he said.

Challenges Remain

The Type 1 Diabetes Grand Challenge, which involves teams from Stanford University, Monash University, Zhejiang University, and more, has poured millions into developing GRIs. The goal is to push the technology into human trials quickly, with the hope that it will be ready for clinical use soon.

While the potential is enormous, the path forward isn’t without challenges. Developing glucose-sensitive insulin that performs as well in humans as it does in animals will require further testing and refinement.

Scientists still need to fine-tune the insulin to ensure that it works reliably across a broad range of blood sugar levels, as not all diabetes patients have the same needs. The cost of developing such a novel treatment also raises questions about accessibility — especially in the U.S. where even traditional insulin is ridiculously expensive.

Despite these hurdles, the momentum behind glucose-responsive insulin is building. Biomedical engineers working on similar insulins believe it’s only a matter of time before we see smart insulin therapies tailored to individual needs.

If the research continues to deliver on its promise, the future for people with diabetes may look very different. No longer would they need to constantly adjust their insulin doses to keep blood sugar in check. Instead, their insulin would do the work for them — precisely, automatically, and safely. It’s not a cure, but it may be the closest science has come yet.