Drugs like Ozempic and Zepbound have changed the conversation around weight loss and diabetes. But for many users, the benefits come with a frustrating downside: nausea. In fact, up to 70% of people stop taking GLP-1 medications within a year due to gastrointestinal distress.
Now, researchers at Syracuse University say they may have found a way to bypass that problem altogether.
In a new study published in Science Translational Medicine, a multidisciplinary team led by medicinal chemist Robert Doyle, PhD, identified a different part of the brain that may hold the key to appetite control, support cells, not neurons. And their new compound, TDN, appears to activate those cells directly, triggering weight loss without the queasy side effects.
“Instead of running a marathon from the very beginning like current drugs do, our targeting downstream pathways in support cells is like starting the race halfway through, reducing the unpleasant side effects many people experience,” Doyle said.
Most current medications, like GLP-1 receptor agonists, work by activating neurons in the hindbrain that regulate appetite. But Doyle and his team looked further at the glial and astrocyte support cells that surround and assist neurons. These cells, long considered “background players,” may actually produce molecules that regulate hunger themselves.
One such molecule is octadecaneuropeptide (ODN). In earlier tests, researchers found that injecting ODN directly into rats’ brains reduced appetite and improved glucose processing. But because direct brain injection isn’t practical in humans, the team developed TDN, a more drug-friendly version of the molecule that can be given via regular injection.
When tested in obese mice and musk shrews, TDN promoted weight loss and improved insulin sensitivity, without causing nausea or vomiting.
That’s a big deal, Doyle said, because it points to an entirely new way of regulating appetite. Instead of working through the typical neuron-based pathway, TDN activates a more targeted “shortcut,” bypassing the sequence of reactions that often lead to side effects.
“If we could hit that downstream process directly,” Doyle said, “then potentially we wouldn’t have to use GLP-1 drugs with their side effects. Or we could reduce their dose, improving the toleration of these drugs.”
The implications extend beyond weight loss. Because TDN also improved glucose control in lab animals, it could eventually be useful in treating type 2 diabetes and other metabolic conditions.
To move this work toward the clinic, the team has launched a company called CoronationBio, which has licensed the intellectual property from Syracuse University and the University of Pennsylvania. Human trials are expected to begin in 2026 or 2027, depending on regulatory progress and development partnerships.
For now, the discovery represents a promising shift in the science of appetite regulation, one that moves beyond neurons and possibly beyond nausea.
This study was conducted at Syracuse University in collaboration with SUNY Upstate Medical University. The research is supported by Syracuse University and private funding through CoronationBio.