Researchers across the U.S. believe they may have developed a groundbreaking weight loss treatment that could challenge popular drugs like Ozempic and Wegovy—but without the nausea, vomiting, and other debilitating side effects that cause many patients to abandon treatment.
Dr. Robert Doyle, a medicinal chemist and professor at Syracuse University, has spent years working on two promising peptide compounds—GEP44 and KCEM1—alongside Dr. Matthew Hayes from the University of Pennsylvania and Dr. Christian Roth from Seattle Children’s Research Institute. These compounds, introduced at recent conferences for the American Chemical Society and The Obesity Society, could reshape the weight loss drug market if human trials prove successful.
A Different Approach to Weight Loss
Unlike existing GLP-1 receptor-targeting drugs, which often trigger nausea and other gastrointestinal discomfort, Doyle’s research takes a new route. His team is focusing on PYY receptors, which are linked to appetite regulation but appear to avoid the same unpleasant side effects.
“Our approach has been to partner with PYY receptors,” Doyle told Newsweek, “and we’re finding that we can trigger significant weight loss with essentially no nausea or vomiting.”
This could be a major breakthrough. A study from Blue Health Intelligence in May 2024 found that over 30 percent of patients prescribed GLP-1 drugs quit treatment within the first four weeks due to side effects. Other research has put discontinuation rates as high as 74 percent within the first year. For many, the decision to stop isn’t about effectiveness—it’s about quality of life.
Why the Market Needs More Competition
Doyle and his colleagues have already filed patents and are actively working to bring their discoveries to market. They have also formed a company—co-owned by Syracuse University and the University of Pennsylvania—to develop and commercialize these compounds. While the team is keeping the company’s name private for now, they confirm they have investors and expect to begin human trials within the next year.
If successful, these drugs could offer a much-needed alternative in a market currently dominated by just a few medications.
- Wegovy and Ozempic, both made by Novo Nordisk, have been some of the most widely used weight loss drugs.
- Demand for these medications has skyrocketed, leading to shortages and high prices.
- Some patients are paying more than $1,000 a month out of pocket for weight loss prescriptions.
“Monopoly is never good,” Doyle said. “And a monopoly of a new drug, in a new class, in a new field is going to be astronomically expensive.”
Skepticism Remains
Not everyone is convinced that these new compounds will be free of gastrointestinal side effects.
Dr. Satya Jonnalagadda, vice president of scientific and clinical affairs at Medifast, remains cautious. She pointed out that gastrointestinal issues have long been a challenge in weight loss medications.
“Given the peptides that are being looked at, GI will continue to be a major side effect, because these are hormones that are acting on your gut,” Jonnalagadda explained.
She also emphasized that even if side effects are reduced, maintaining long-term weight loss requires more than just medication. Studies have shown that people who stop taking Wegovy or Ozempic often regain lost weight. A holistic approach that includes lifestyle and nutritional changes is key.
Are Side Effects Overblown?
While some doctors warn about high dropout rates due to side effects, others argue that these concerns may be exaggerated.
Dr. Holly Lofton, director of the medical weight management program at NYU Langone Health, told Newsweek that in clinical trials, fewer than 5 percent of patients discontinued GLP-1 drugs due to gastrointestinal issues.
“You hear a lot about side effects, but most people don’t have side effects,” Lofton said. “It’s just that those who do have side effects are quite loud about it, and I find that those who don’t have side effects stay under the radar and keep taking their medication and do well.”
Still, if Doyle’s compounds can match the effectiveness of existing treatments without the risk of nausea, they could change the conversation around weight loss medication.
What’s Next for GEP44 and KCEM1?
With human trials expected to begin within a year, Doyle’s team remains optimistic.
“Patients want to lose weight, but they don’t want to feel sick doing it,” Doyle said. “Our approach since day one has been to try and see if we can do this without making people feel sick in the process.”
If successful, these compounds could become the next major development in weight loss treatment—offering a real alternative for those who have struggled with the side effects of existing medications.
