New method can cut Ozempic dose by 75%

According to a study presented by the American Chemical Society at a spring meeting in San Diego in San Diego, a new drug delivery system that will directly apply to antibodies can allow patients to use only one-quarter of the typical GLP-1 dose while achieving better, more lasting results.

This innovation is at a critical moment as the nationwide shortage of popular GLP-1 drugs such as Ozempic and Wegovy has made many patients work hard to maintain treatment options. In addition to solving supply issues, the approach can reduce the cost of these expensive drugs that may run thousands of dollars a year without insurance coverage.

In mouse studies, the novel delivery system maintained blood sugar control and weight loss for up to 15 days after one treatment, while significantly fewer drugs were used than standard methods.

“With new technologies like this, the future of peptide-based therapies could reduce costs and increase efficiency,” said Bradley Pentelute, professor of chemistry at Massachusetts Institute of Technology who leads the research team.

Use the human body’s own resources

GLP-1 drugs have changed diabetes treatment and weight management, but they face a fundamental challenge: As peptide-based drugs, they are easily broken down by enzymes in the body, limiting their effectiveness and requiring frequent injections.

Previous attempts to extend its lifespan involve fusing GLP-1 drugs into antibodies in a laboratory setting, an effective but expensive process requiring the extraction and modification of antibodies from patients in vitro.

Pentelute’s team took a different approach to what he called “in vivo antibody painting.” Instead of extracting antibodies, their systems provide a specially designed peptide that connects GLP-1 drugs directly to immunoglobulin G (IgG) antibodies circulating in the blood.

The system consists of three components: a binder region attached to the antibody, a payload region with GLP-1 drug, and a reactive region that creates a strong chemical bond between the drug and the antibody. This converts antibodies that occur naturally in the body into drug delivery vehicles.

Promising early results

Laboratory tests show that almost half of all antibodies successfully bonded to GLP-1 drugs at normal body temperature. Results are even more promising when tested in mice with type 2 diabetes and obesity.

Not only did the mice maintain blood sugar control and weight loss for up to 15 days after one treatment, they actually showed better and more sustained results than mice receiving traditional GLP-1 administration – although only one-quarter of the standard dose.

These findings have been shared in preprint research articles currently being peer-reviewed. In the ACS demonstration, Pentelute also revealed new results that show that the system can effectively map antibodies even in the presence of cellular proteins and other biological materials.

Beyond weight loss

The MIT team is already exploring the wider application of its antibody painting technology.

“We are also expanding the technology to enable antibody drugs to bind cancer to cancer,” Pentelute shared in his speech. “And we are modifying this technology to be able to coat multiple drugs into one antibody.”

This versatility suggests that the approach may have the potential to alter treatments for a variety of diseases other than diabetes and obesity.

Although the study is still in its early stages (still in human trials), it represents a promising direction to address supply challenges and high costs, with limited access to these increasingly popular drugs.

The study was funded by Pentelute at the National Cancer Institute of National Institutes of National Institutes of National Institutes of Health. The temporary patent for the technology is being tried from MIT.