Gut-Targeted TAS2R Agonist Reduces Hunger and Promotes Weight Loss

The global epidemic of obesity and related metabolic disorders continues to pose significant health challenges, with current pharmacotherapies often limited by systemic side effects. Targeting gut-specific pathways offers a promising avenue to mitigate these issues. This study investigates the potential of a novel, gut-restricted compound, ARD-101, as a therapeutic agent. Specifically, this research addresses whether a gut-restricted TAS2R agonist can effectively reduce hunger in adults and promote weight loss in preclinical models, especially when combined with DPP-4 inhibition.

In the human study, ARD-101 significantly reduced subjective hunger scores by 25% (p<0.01) compared to placebo, with effects sustained for up to 6 hours. In DIO mice, ARD-101 monotherapy led to a 7% reduction in body weight (p<0.05) over 14 days, alongside a 15% decrease in daily food intake. The combination therapy proved even more effective: > Mice treated with ARD-101 plus a DPP-4 inhibitor exhibited a remarkable 12% body weight loss (p<0.001), representing a 70% greater reduction than ARD-101 alone and a 2.5-fold improvement over the DPP-4 inhibitor monotherapy. This synergistic effect was accompanied by a 22% reduction in food intake and improved glucose tolerance, with fasting glucose levels decreasing by 18% (p<0.01).