Weight loss and diabetes drugs currently available, such as Ozempic and Zepbound, often fail to provide lasting results. While GLP-1 drugs work by targeting brain neurons that regulate appetite, they frequently cause unpleasant side effects. According to researchers, nausea and vomiting force 70% of patients to stop treatment within a year.
Now, a Syracuse University-led research team believes they’ve found a new approach that could offer weight loss without the gastrointestinal distress that derails so many patients.
Dr. Robert Doyle, a medicinal chemist and the Jack and Laura H. Milton Professor of Chemistry in the College of Arts and Sciences at Syracuse University, is leading the effort. Dr. Doyle is also a professor of pharmacology and medicine at SUNY Upstate Medical University. He and his colleagues have identified a different brain target — one that focuses on cells supporting neurons rather than the neurons themselves. This breakthrough could help treat both obesity and diabetes in a safer, more tolerable way.
Looking beyond neurons
For decades, neurons have been the most obvious and well-studied targets for brain-related drug development. GLP-1 medications, for example, zero in on neurons in the hindbrain that control appetite. But Dr. Doyle’s team is taking a different route, exploring the role of “support” cells, including glia and astrocytes, which may also influence hunger and metabolism.
A recent collaborative research effort has found that these support cells play a role in reducing feelings of hunger, although this process has received far less attention in the scientific literature. Dr. Doyle explains:
We wanted to know whether support cells might produce new peptides or new signaling molecules that might be critical in body weight reduction.
How it works
To visualize the difference between neurons and their support cells, Dr. Doyle offers a simple analogy:
Think of each brain neuron as a light bulb and support cells as the components that allow the light bulb to brighten, including the wiring, switch and filament. All of those supporting parts beyond the light bulb play a role in making the light shine.
In their research, the team discovered that certain support cells in the hindbrain naturally produce a molecule called octadecaneuropeptide (ODN), which can suppress appetite. In lab experiments, when ODN was injected directly into the brains of rats, the animals lost weight and improved their glucose processing, an important factor for managing diabetes.
However, injecting substances directly into the brain isn’t a realistic option for human treatment. To solve this, the researchers engineered a new version of the molecule, tridecaneuropeptide (TDN), that could be administered via regular subcutaneous injections, much like existing GLP-1 treatments.
When tested in obese mice and musk shrews, TDN led to weight loss and improved insulin sensitivity without triggering the nausea and vomiting commonly seen with GLP-1 drugs.
A shortcut to appetite control
One of the team’s key objectives is to develop weight loss therapies that avoid stimulating neurons directly. TDN accomplishes this by bypassing neurons and targeting the downstream support cells responsible for appetite suppression.
Dr. Doyle likens the process to starting a race partway through rather than at the very beginning. He says:
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… If we could hit that downstream process directly, 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. We could trigger weight loss signals that happen later in the pathway more directly.
This “shortcut” approach could have major implications for the millions struggling with obesity or type 2 diabetes, particularly those who cannot tolerate current treatments.
From lab to clinic
To turn this scientific discovery into a practical therapy, a new company called CoronationBio has been launched. The company has licensed intellectual property related to ODN derivatives for treating obesity and cardio-metabolic disease from both Syracuse University and the University of Pennsylvania.
CoronationBio’s mission is to move promising candidates like TDN from the lab into clinical trials. They are collaborating with other companies in the biotech and pharmaceutical sectors to accelerate development, with hopes of starting human trials as early as 2026 or 2027.
If successful, the new treatment could address one of the biggest barriers in obesity care: Keeping patients on their medication long enough to see lasting benefits.
The future of appetite control
While the research is still in early stages, Dr. Doyle’s team is optimistic about the potential impact. By shifting the focus from neurons to their support cells, they hope to change how scientists and clinicians approach weight management and metabolic disease.
The concept isn’t just about creating a new drug; it’s about rethinking the biology behind appetite regulation. Support cells, once considered secondary players in brain function, may hold the key to more tolerable and effective treatments for chronic conditions that affect millions worldwide.
As Dr. Doyle and his colleagues continue refining TDN and preparing for clinical testing, the hope is that this line of research will not only expand treatment options but also offer relief to patients who have long struggled with both their weight and the side effects of current medications.
If their theory holds true in human trials, this could mark the beginning of a new era in weight loss medicine — one where the body’s own support systems are harnessed to promote health, without the misery that forces so many to give up on treatment.
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Source: “Scientists uncover hidden brain shortcut to weight loss without the nausea,” ScienceDaily, 8/10/25
Source: “Shortcut to Weight Loss: No Nausea Required,” Syracuse University, 7/30/25
Source: “Hindbrain octadecaneuropeptide gliotransmission as a therapeutic target for energy balance control without nausea or emesis,” Science Translational Medicine, 7/23/25
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