Keeping blood glucose levels as close to normal as possible is important for people with type 2 diabetes, as it lowers the risk of serious complications. However, despite a long list of treatment options, patients still struggle with glucose control, especially when working out meal-specific doses. Treatments that cut down on injections are seen as a way to overcome this problem. Now, in a paper in Nature Biomedical Engineering, scientists describe a new biopolymer injection that could potentially replace daily or weekly insulin shots with one that need only be given once or twice per month.
Diabetes arises because of a problem with insulin, which is a hormone that is made in the pancreas and which helps cells to absorb glucose so that they can use it for energy.
Although the incidence of newly diagnosed diabetes is starting to drop in the United States, it is still a huge public health problem that affects more than 29 million people.
In 2013, the Centers for Disease Control and Prevention (CDC) suggested that diabetes was the seventh leading cause of death in the U.S., and that more than a fifth of the country’s healthcare costs are for people diagnosed with diabetes.
In their study paper, biomedical engineers from Duke University in Durham, NC, explain that “despite the long list of treatment options,” nearly half of type 2 diabetes cases in the U.S. “are not properly managed.”
The researchers suggest that one reason for such a high rate of failure in the management of type 2 diabetes is that patients struggle to keep to treatment regimens, especially when they are required to frequently deal with complicated meal-specific doses.
Another reason they give is that many of the widely used treatments bring unwanted side effects, such as raising the risk of low blood sugar, known as hypoglycemia, or weight gain.
From a drug development point of view, one of the biggest challenges in treating diabetes is that insulin demands in the body are always changing.
In order to address this challenge, there are now treatments for type 2 diabetes that use a new class of drugs called glucagon-like peptide-1 (GLP1) receptor agonists. These drugs use GLP1, a signaling molecule, to trigger insulin release in the pancreas.
Because GLP1 does not last long in the body, drug developers have used various ways to extend its half-life – such as fusing it with various synthetic and biological compounds. These attempts have succeeded in extending the drug’s active life in the human body for up to a week.
However, the researchers note that despite this improvement, so far none of the current treatments have solved the problem of the drug’s effectiveness gradually decreasing over time.
The new approach that the Duke researchers describe fuses GLP1 with a heat-sensitive biopolymer called elastin-like polypeptide. Held in a solution, the biopolymer drug can be injected into the skin with a normal needle.
Once it is in the bloodstream, the heat of the body causes the biopolymer to form a biodegradable gel that releases the drug slowly and steadily, without the “peaks and troughs” associated with other forms of GLP1 delivery.
Using results from previous work on GLP1 for glucose control, the team tried different molecular designs of the new delivery solution.
They eventually found a design of the biopolymer that could control glucose levels in mice for up to 10 days with a single injection. This was a great improvement on previous attempts, after which the controlled release had only lasted for 2 or 3 days.
In tests on rhesus monkeys, the team found that the optimized formulation resulted in glucose control lasting for more than 14 days from a single injection. Also, the drug was released at a constant rate, without “peaks and troughs,” during the whole period.
Senior author Ashutosh Chilkoti, a professor of biomedical engineering at Duke, says that they “managed to triple the duration of this short-acting drug for type 2 diabetes, outperforming other competing designs.”
At present, patients using dulaglutide – the longest-lasting controlled release treatment for type 2 diabetes – have to inject themselves once per week. Patients on standard insulin treatments must inject themselves at least twice each day.
The team now plans to test the biopolymer on other animals and investigate how the immune system reacts to repeated injections. They also want to find out how well it performs for the controlled release of drugs in other areas, such as pain management.
“What’s exciting about this work was our ability to demonstrate that the drug could last over 2 weeks in non-human primates. Because our metabolism is slower than monkeys and mice, the treatment should theoretically last even longer in humans, so our hope is that this will be the first bi-weekly or once-a-month formulation for people with type 2 diabetes.”
First author Kelli Luginbuhl, Ph.D. student at Duke University