Two-in-one shot helps blood glucose control

Thursday, 14 May 2020

A Stanford research team believe they have found a way to boost the effectiveness of the insulin to help with blood glucose control.

The team, led by scientist Eric Appel, have developed a way to combine insulin with a second hormone known as amylin, to create a two-in-one shot or injection that could, if proven safe in human trials, make it easier for people living with diabetes to control their blood glucose levels.

The role of Amylin

Amylin plays a synergistic role with insulin to control blood glucose levels after eating in a way that is more effective than insulin alone and mimics what occurs naturally with a meal.

While the amylin-based drug is already commercially available, it is estimated that less than 1 percent of people living with diabetes taking insulin therapy also take this complementary treatment because the two hormones – which work together seamlessly in the body – are too unstable to coexist in the same syringe.

“Taking that second injection with the insulin shot is a real barrier for most patients. Our formulation would allow them to be given together in a single injection or in an insulin pump,” said Appel.

Protective coating

The new technique involves a protective coating that wraps around insulin and amylin molecules and, for the first time, allows them to coexist in a single shot.

“This coating dissolves in the bloodstream, enabling these two important hormones to work together in a way that mimics how they function in healthy individuals,” Appel said.

So far, the researchers have tested the wrapper’s stability in the laboratory, and done preliminary experiments to see how their two-in-one injection works on the most advanced preclinical model – diabetic pigs. But, because both drugs are already on the market and the dual-drug formulation was tested in advanced models, Appel said the team need only demonstrate that their technique is nontoxic in humans to start trials in people, bringing this technology closer to market than most early-stage drugs.

Appel and his collaborators hope this approach could, one day, dramatically increase the use of amylin and lead to improved glucose management for the estimated 450 million people worldwide with type 1 or type 2 diabetes.

“Although few people living with diabetes currently take the amylin-based drug after their insulin injection, those who do experience profound benefits,” Appel said.

Past clinical data shows that patients taking both lose weight and have better control over their blood glucose. Enhanced diabetes management can reduce the risk of serious health complications, such as kidney failure, blindness, heart disease and amputations, all of which loom over anyone with diabetes.

Mimicking the body

If the wrapper approach makes it possible to combine insulin and amylin in one dose, this would offer people living with diabetes a convenient way to mimic their natural secretion in the human body. For people without diabetes, amylin is secreted from the same cells in the pancreas that produce insulin. Insulin improves the uptake of sugar by cells, removing it from the bloodstream. For its part, amylin does three things to control blood glucose. First, it stops another hormone, glucagon, from telling the body to release additional glucose that has been stored in the liver. Second, it produces a sense of “fullness” at mealtimes that reduces food intake. Third, it actually slows the uptake of food by the body, reducing the typical spike in blood glucose after a meal. All three are a boon to diabetes care.

What’s next?

In animal studies, the researchers saw significant overlap of the activity of the dual-drug formulation, an important finding that indicates the approach is closely mimicking what happens in a healthy body – including a near-total suppression of glucagon, the hormone that tells the liver to release stored glucose, even though the person has just consumed a meal.

“We’re excited about the results to say the least,” Appel said. The team has already filed for a patent on the technology.

The study was published May 11 in Nature Biomedical Engineering.

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