By Clinical Research News Staff 

November 6, 2025 | Developing a “super-tolerable” weight loss drug is one of the biggest challenges in obesity medicine today. Robert Doyle, Ph.D., Syracuse University chemistry professor and a professor of pharmacology and medicine at SUNY Upstate Medical University, and his lab recently reported the creation of a promising molecule, tridecaneuropeptide (TDN), which reduces food intake without triggering the awful side effects often associated with glucagon-like peptide-1 (GLP-1) drugs such as Ozempic and Zepbound. 

TDN was developed when a colleague suggested looking into astrocytes, the brain cells that support neurons and may play a key role in regulating appetite. Unlike GLP-1 drugs, which act through neuronal pathways and can cause nausea, vomiting, and fatigue, TDN targets astroglial support cells in the hindbrain. Early preclinical findings, published in Science Translational Medicine (DOI: 10.1126/scitranslmed.adu6764), show appetite suppression and weight loss across three animal models—obese mice, rats, and musk shrews—without the adverse effects tied to GLP-1 therapies. It also does not trigger insulin secretion, unlike GLP-1 drugs. 

The molecule itself is a truncated version of an endogenous neuroprotective peptide called octadecaneuropeptide (ODN), which is naturally produced in the brain. Doyle’s team synthesized and tested hundreds of variations before identifying TDN and a longer-acting companion peptide as promising candidates. The team is now working on modifying TDN to make it more stable, long-acting, and capable of crossing the blood-brain barrier—critical steps before human testing can begin. 

Translating an optimized TDN candidate into the clinic is being advanced by Coronation Bio, a spinout company co-founded by Doyle that has licensed intellectual property from Syracuse and the University of Pennsylvania. The company is preparing for Investigational New Drug (IND) application-enabling studies, which involve rigorous preclinical testing to satisfy U.S. Food and Drug Administration requirements. If successful, first-in-human clinical trials could launch as early as 2027. 

Clinical development will likely mirror existing injectable GLP-1 regimens, with weekly subcutaneous doses in the abdomen, thigh, or arm. Taking peptides orally is “a bridge beyond us right now,” Doyle notes, citing the limited uptake of Rybelsus, an oral version of semaglutide, due to higher frequency of gastrointestinal side effects. 

Beyond tolerability, TDN research highlights a broader shift in obesity drug development: the pursuit of therapies that avoid the rebound weight gain seen when patients discontinue GLP-1s. Most patients stop treatment within months because side effects escalate with higher doses. Doyle and colleagues hope TDN’s distinct mechanism of action will enable safer, longer-term use and improved quality of life. 

To read the full story written by Deborah Borfitz, head on over to Bio-IT World News.