GLP-1 medications such as Ozempic and Wegovy have changed the way obesity is treated, but many patients face difficulty keeping weight off once they stop using these drugs. George Mason University has started a new clinical trial to address this issue.
The university is among six research sites in the United States running a Phase 2 trial for ARD-201, a drug created by Aardvark Therapeutics. Unlike injectable GLP-1 medications that help with rapid weight loss, ARD-201 is an oral drug being tested for its ability to regulate appetite and maintain weight after patients discontinue injectables. The medication activates bitter taste receptors in the gut and brain without causing an actual bitter taste, signaling the body to eat less.
"It's almost a survival instinct," said Lawrence Cheskin, an obesity researcher and professor who leads the George Mason site for the trial. "When something tastes bitter, the body assumes there may be a toxin, so you back off."
Cheskin explained that this mechanism might help reduce appetite in a more subtle way than injectables. "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 study will recruit adults who lost weight with injectable medications but have since stopped them. Researchers plan to observe how much weight participants regain and compare their results with published data on typical patterns of post-injectable weight regain. This open-label Phase 2 trial does not include a placebo group; all participants know they are taking ARD-201.
Previous research has informed this current effort. A similar compound called ARD-101 was earlier studied for Prader-Willi syndrome—a rare disorder characterized by intense hunger—and now ARD-201 is being investigated as an oral therapy for wider use in obesity management.
Cheskin noted that George Mason was chosen as a trial site due to its history of expertise in obesity research and clinical care. If this Phase 2 study yields positive results, it could lead to larger trials designed to rigorously test whether ARD-201 helps maintain long-term weight loss.
