Researchers Present Ozempic Alternatives—Without Sickening GI Side Effects

Researchers from across the country believe they have developed a breakthrough weight loss drug treatment: two new peptide compounds that could rival popular drugs like Ozempic and Wegovy, but without some of the debilitating side effects. Dr. Robert Doyle, a medicinal chemist and professor at Syracuse University in New York, has been working on the compounds—GEP44 and KCEM1—for several years along with his collaborators, Dr. Matthew Hayes, vice chair for basic and translational neuroscience research at the University of Pennsylvania's Perelman School of Medicine, and Dr. Christian Roth, an endocrinologist at Seattle Children's Research Institute. Recently, they've introduced the compounds at conferences for the American Chemical Society and The Obesity Society. These compounds take a different approach to weight loss than existing medications, which can cause nausea, vomiting and gastric malaise. GLP-1 receptor targeting has been successful for weight loss but can trigger an "unwell" feeling that leads many patients to abandon treatment, Doyle told Newsweek. "Our approach has been to partner with PYY receptors," Doyle said, "and we're finding that we can trigger significant weight loss with essentially no nausea or vomiting." More than 30 percent of patients that are prescribed GLP-1 drugs drop out of treatment in the first four weeks, according to a May 2024 study from Blue Health Intelligence. Researchers found that nearly all new GLP-1 users suffered from some kind of gastrointestinal side effect, leading to "treatment failure" and "wasted expense" for some patients. Other studies have pinned discontinuation rates as high as 74 percent in the first year of treatment.

Doyle and his colleagues have already filed patents and are actively working to bring their new discoveries to market. They have also formed a company, co-owned by Syracuse University and the University of Pennsylvania, to further develop and commercialize the compounds. (Doyle declined to share the name of the company, saying they are keeping it "dark" for now—but that they do have investors.) The researchers aim to begin human trials within the next year: a significant step toward FDA approval. "There's a lot of investment going into this field," Doyle said. "A lot of people are looking for the next great weight loss drug." The current weight loss drug market has been dominated by a handful of medications despite ample space for new treatments. Doyle believes that introducing new options could make weight loss drugs more affordable and accessible for patients—especially for those who are paying upwards of $1,000 a month for their medication. "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."

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Despite the excitement surrounding these new discoveries, some experts remain cautious. Dr. Satya Jonnalagadda, vice president of scientific and clinical affairs at weight loss company Medifast, pointed out that gastrointestinal issues have long been a challenge for weight loss drugs. "Given the peptides that are being looked at, GI will continue to be a major side side effect, because these are hormones that are acting on your gut," Jonnalagadda said. "Hopefully with the molecules that are in the pipeline, we may see some positive outcomes in the future." Jonnalagadda also warned that discontinuation rates remain high across the board—emphasizing the need for a multidisciplinary approach that includes lifestyle and nutritional interventions. Studies have shown that patients are likely to regain the weight they lost after stopping Wegovy or Ozempic. On the other hand, Dr. Holly Lofton told Newsweek that she dispels a lot of myths about GLP-1 drugs as director of the medical weight management program at NYU Langone Health. In her experience, side effects are not as common as people think they are. In clinical trials, fewer than 5 percent of patients discontinued a GLP-1 due to gastrointestinal side effects. "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." Doyle and his team remain optimistic that their research will fill gaps in the current market. "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."