GLP-1 medications like Ozempic and Wegovy have transformed obesity treatment, but maintaining weight loss after the medications stop remains a challenge. George Mason University is leading a new clinical trial that may help people sustain their results.
The university is one of six research sites across the U.S. administering a Phase 2 clinical trial of ARD-201, a novel weight-maintenance drug developed by Aardvark Therapeutics that works differently from existing obesity medications. Unlike injectable medications that drive significant short-term weight loss, ARD-201 is being studied for its potential role in appetite regulation and weight maintenance after injectable therapy ends. The oral medication works by activating the bitter taste receptors in the gut and brain without creating an actual bitter taste, signaling the body to eat less.
"It's almost a survival instinct," said Lawrence Cheskin, obesity researcher, professor, and past chair of Nutrition and Food Studies, who is leading the George Mason research site for the trial. "When something tastes bitter, the body assumes there may be a toxin, so you back off."
By subtly triggering that signal, the drug appears to reduce appetite without the dramatic effects associated with injectable medications. "This isn't going to cause large weight loss on its own," Cheskin said. "The question is whether it can help people keep weight off."
The trial will enroll adults who previously lost weight using injectable medications and have since stopped them. Researchers will track how much weight participants regain over time and compare outcomes with published data showing typical patterns of weight regain after injectables are ceased. The study is an open-label Phase 2 trial, meaning participants know they are receiving the drug, and there is no placebo comparison group.
Earlier research helped lay the groundwork for the current study. A closely related compound, ARD-101, was previously tested for treating Prader-Willi syndrome, a rare genetic condition marked by extreme, chronic hunger. ARD-201 is now under investigation as an oral therapy for broader obesity and weight-management use.
George Mason was selected as a trial site based on its longstanding expertise in obesity research and clinical weight management, according to Cheskin. If results from this Phase 2 study are promising, they could inform larger, randomized trials to more rigorously test the drug's effectiveness for long-term weight maintenance.
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