Researchers are developing two novel peptide compounds, GEP44 and KCEM1, as potential alternatives to popular weight loss drugs like Ozempic and Wegovy. These compounds aim to reduce the debilitating gastrointestinal side effects often associated with GLP-1 receptor agonists, potentially improving patient adherence and treatment outcomes.
Dr. Robert Doyle, a medicinal chemist and professor at Syracuse University, along with collaborators Dr. Matthew Hayes from the University of Pennsylvania and Dr. Christian Roth at Seattle Children's Research Institute, have presented these compounds at conferences for the American Chemical Society and The Obesity Society. Their approach differs from existing medications by targeting PYY receptors in addition to, or instead of, GLP-1 receptors.
Targeting PYY Receptors for Weight Loss
"Our approach has been to partner with PYY receptors," Dr. Doyle stated, "and we're finding that we can trigger significant weight loss with essentially no nausea or vomiting." This is a significant departure from GLP-1 receptor targeting, which, while effective for weight loss, often leads to gastrointestinal distress that causes many patients to discontinue treatment. A May 2024 study from Blue Health Intelligence indicated that over 30% of patients prescribed GLP-1 drugs drop out of treatment within the first four weeks, with nearly all new users experiencing some form of gastrointestinal side effect.
Other studies have reported discontinuation rates as high as 74% within the first year of GLP-1 treatment, highlighting a critical unmet need for weight loss medications with improved tolerability. The researchers have filed patents and formed a company co-owned by Syracuse University and the University of Pennsylvania to further develop and commercialize GEP44 and KCEM1. Human trials are projected to begin within the next year, marking a crucial step toward potential FDA approval.
Addressing the Affordability and Accessibility of Weight Loss Drugs
Dr. Doyle believes that introducing new options could make weight loss drugs more affordable and accessible, particularly given the high cost of current medications, which can exceed $1,000 per month. "Monopoly is never good," Dr. Doyle noted, emphasizing that competition in the market could drive down prices and improve patient access.
Expert Perspectives on GI Side Effects and Treatment Adherence
While the new compounds show promise, some experts remain cautious. Dr. Satya Jonnalagadda, vice president of scientific and clinical affairs at Medifast, pointed out that gastrointestinal issues have historically been a challenge for weight loss drugs. He also emphasized the need for a multidisciplinary approach that includes lifestyle and nutritional interventions, as studies have shown that patients often regain weight after discontinuing medications like Wegovy or Ozempic.
Conversely, Dr. Holly Lofton, director of the medical weight management program at NYU Langone Health, stated that, in her experience, side effects from GLP-1 drugs are not as common as perceived. She noted that in clinical trials, fewer than 5% of patients discontinued GLP-1 treatment due to gastrointestinal side effects.
Future Directions
Doyle and his team are optimistic that their research will address the current gaps in the market by providing effective weight loss solutions with improved tolerability. "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."
