An innovative oral therapy for obesity, SYNT-101, has shown encouraging preliminary results in its first human trial. Developed by Syntis Bio, this once-daily treatment aims to replicate the metabolic benefits of gastric bypass surgery by redirecting nutrient absorption to the lower intestine. The study, presented at the European Congress on Obesity in Malaga, Spain, highlights SYNT-101’s potential to safely enhance weight loss and metabolic regulation while preserving lean muscle mass. Participants experienced no adverse effects, and early findings indicate a strong safety profile along with effective modulation of hunger-related hormones.

SYNT-101 works by creating a temporary polydopamine coating in the duodenum, effectively excluding nutrients from being absorbed in the upper part of the small intestine. This mechanism shifts nutrient exposure further down the digestive tract, mimicking the physiological changes seen after gastric bypass procedures. According to Rahul Dhanda, CEO of Syntis Bio, the drug could provide a convenient alternative to existing therapies like GLP-1 receptor agonists, which often come with gastrointestinal side effects and concerns about long-term maintenance. Preclinical studies demonstrated significant weekly weight loss without compromising lean muscle mass, making it a potentially groundbreaking option for managing obesity.

In the pilot study involving nine healthy participants, researchers administered varying doses of SYNT-101 in liquid form. Safety assessments included endoscopic imaging to confirm the formation of the polydopamine lining and blood tests to evaluate hormone levels associated with satiety and metabolism. Results indicated that the coating formed successfully and was naturally cleared within 24 hours. Furthermore, there were no reported adverse events across all dosage groups, reinforcing the compound's tolerability.

Blood glucose tolerance tests revealed delayed glucose absorption following treatment, aligning with the intended redirection of nutrient processing. Specifically, glucose uptake was reduced by approximately 35% and 21% at 30 and 60 minutes post-treatment, respectively. These findings suggest that SYNT-101 effectively modifies where nutrients are absorbed, promoting feelings of fullness and supporting metabolic balance. Additionally, hormonal changes consistent with decreased appetite were observed, including elevated leptin levels and reduced ghrelin concentrations.

The positive outcomes of this initial investigation pave the way for more extensive clinical trials. While the current study did not focus on measuring weight loss directly, the hormonal responses noted align closely with preclinical data indicating reduced food intake. Syntis Bio anticipates filing an Investigational New Drug application with the FDA later in 2025, underscoring their commitment to advancing this promising therapy. By preserving muscle mass while reducing fat stores and enhancing natural satiety signals, SYNT-101 holds great promise as a safe and sustainable solution for individuals struggling with obesity.