New Method Could Slash Ozempic Doses by 75%

A new drug delivery system that “paints” weight loss medications directly onto antibodies could allow patients to use just one-fourth of their typical GLP-1 dose while achieving better, longer-lasting results, according to research presented Sunday at the American Chemical Society’s spring meeting in San Diego.

The innovation comes at a critical time, as nationwide shortages of popular GLP-1 medications like Ozempic and Wegovy have left many patients struggling to maintain their treatment regimens. Beyond addressing supply issues, the approach could potentially reduce costs for these expensive medications, which can run patients thousands of dollars annually without insurance coverage.

In mouse studies, this novel delivery system maintained blood sugar control and weight loss for up to 15 days after a single treatment—all while using significantly less medication than standard methods.

“With new technology like this, the future of peptide–based therapies could see reduced costs and enhanced effectiveness,” said Bradley Pentelute, professor of chemistry at the Massachusetts Institute of Technology, who led the research team.

Working With the Body’s Own Resources

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

Previous attempts to extend their lifespan have involved fusing GLP-1 drugs to antibodies in laboratory settings—an effective but expensive process requiring extraction and modification of a patient’s antibodies outside the body.

Pentelute’s team took a different approach with what he calls “in vivo antibody painting.” Rather than extracting antibodies, their system delivers a specially designed peptide that attaches GLP-1 medications directly to immunoglobulin G (IgG) antibodies circulating in the bloodstream.

The system consists of three components: a binder region that attaches to the antibody, a payload region carrying the GLP-1 drug, and a reactive region that creates a strong chemical bond between the medication and antibody. This transforms the body’s naturally occurring antibodies into drug delivery vehicles.

Promising Early Results

Laboratory tests showed that nearly half of all antibodies successfully bonded with GLP-1 medications at normal body temperature. When tested in mice with Type 2 diabetes and obesity, the results were even more promising.

The mice not only maintained blood glucose control and weight loss for up to 15 days after a single treatment, but they actually showed better and more sustained results than those receiving traditional GLP-1 administration—despite receiving only a quarter of the standard dose.

These findings have been shared in a preprint research article currently undergoing peer review. At the ACS presentation, Pentelute also revealed new results showing the system can effectively paint antibodies even in the presence of cellular proteins and other biological material.

Beyond Weight Loss

The MIT team is already exploring broader applications for their antibody painting technology.

“We’re also expanding the technology to make antibody drug conjugates for cancer,” Pentelute shared during his presentation. “And we’re modifying this technology to be able to paint multiple drugs onto one antibody.”

This versatility suggests the approach could potentially transform treatment for multiple conditions beyond diabetes and obesity.

While the research remains in early stages—with human trials still ahead—it represents a promising direction for addressing both the supply challenges and high costs that have limited access to these increasingly popular medications.

The research was funded by Pentelute’s discretionary funds at MIT and the National Cancer Institute at the National Institutes of Health. A provisional patent for the technology is pending from MIT.