Diabetes: Hydrogel system for GLP-1 agonists may reduce injection need

Evan Walker
Evan Walker TheMediTary.Com |
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A new drug delivery system could reduce the frequency of shots required to manage type 2 diabetes. John Fredricks/NurPhoto via Getty Images
  • Dealing with daily or weekly injections may become a thing of the past for people with diabetes if the results of a new study in rats are confirmed in human trials.
  • The study describes a specially formulated hydrogel that could release GLP-1 agonist medications slowly over months.
  • A single injection of a hidden “depot” of hydrogel delivered medications for 42 days in rats, which corresponds to about four months for humans.
  • One risk, however, is that adverse effects would last just as long should they occur.

Many people with type 2 diabetes are taking GLP-1 agonist medications such as Ozempic and Wegovy for glucose management and weight maintenance. However, rigorously sticking to their daily or weekly injections of the drug has proven difficult.

A new study explores the use of hydrogels that allow for time-released doses of GLP-1 drugs that would spare type 2 diabetes patients from having to get injections so frequently.

One injection of medication of a GLP-1-laced hydrogel can deliver doses of the drug for 42 days in rats, which is equivalent to roughly four months in humans, according to the researchers. If this result is confirmed in human trials, type 2 diabetes patients might need only three injections a year instead of the many more they now require.

While hydrogels are not new — contact lenses, for example, are made from hydrogels — the researchers’ formulation is novel. The hydrogel delivers either semaglutide or liraglutide.

The hydrogel is a loose mesh of polymer chains, nanoparticles, and drug molecules.

It has just enough of a fluid-like flow that injections may be performed using standard off-the-shelf needles. Even so, the hydrogel melts away slowly over a period of months, releasing doses of medication at the desired intervals.

The hydrogel/medication mix is administered as a small dollop — called a “depot” — under the skin in a conveniently out-of-the-way, unbothersome location. The researchers anticipate a depot may range from 0.5 ml to 1.25 ml in size.

The engineering challenge for the authors was developing a depot small enough to be unobtrusive for patients, and yet resilient enough to last for four months, and large enough to hold a sufficient amount of hydrogel and medication.

Four months was selected as the team’s target, as it matches the frequency with which they say people with type 2 diabetes see their physicians.

The study is published in Cell Reports Medicine.

Both of the drugs tested in the study were GLP-1 agonists. However, only liraglutide is currently approved for use in children ages 12–17 years with obesity. In addition, the two medications behaved differently in the study’s testing.

The researchers found that immediately following semaglutide delivery, too much of the drug was released, resulting in concerns that this would not be well-tolerated. For liraglutide, however, the dosing was more consistent over the study period.

One study found that after a year on GLP-1 agonist drugs, only about half of type 2 diabetes patients were adhering to their prescribed schedule of injections.

“We showed that a single hydrogel-based drug product performed similarly to 42 daily injections of a standard commercial drug product — we showed the gels were actually a bit better. This reduction in the number of required shots constitutes an enormous reduction in the burden of treatment.”
— Dr. Eric Appel, the study’s corresponding author, associate professor of materials science & engineering a Stanford University, speaking to Medical News Today.

Dr. Appel said the consistency offered by the hydrogel may carry an additional benefit:

“Our results indicate that the more consistent exposure to the main liraglutide or semaglutide drugs by continuous slow release from the hydrogels actually improves glucose management compared to daily injections of the standard drugs.”

Dr. Matthew Webber, Keating-Crawford collegiate professor of engineering and associate professor of chemical and biomolecular engineering at the University of Notre Dame, who was not involved in the study, agreed: “Injectable hydrogels are a promising class of materials for the delivery and controlled release of therapeutic compounds.”

Dr. Webber cautioned, however, about the “large mass of ‘inactive’ matter that is entailed in a hydrogel formulation, potentially leading to concerns regarding cost to manufacture the therapy or accumulation in the body. Such factors must be carefully considered in hydrogel design.”

Dr. Sumera Ahmed, board certified in internal medicine and assistant professor at Touro University, who was also not involved in the study, said that “a 4-month-long duration seems extended” considering potential side effects.

“If an individual develops side effects, then this could be long-lasting until the medication effect wears off,” said Dr. Ahmed.

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