New Obesity Pill Mimics Gastric Bypass Without Surgery

SYNT-101 introduces an innovative method for weight loss by temporarily redirecting nutrient absorption in the small intestine.

A groundbreaking new obesity treatment in pill form is showing exciting early promise. In a first-of-its-kind human study, researchers tested SYNT-101, a once-daily oral medication designed to safely and effectively shift nutrient absorption to the lower intestine. This process mimics how gastric bypass surgery helps people lose weight and manage metabolism, without the need for surgery.

The study, presented at the European Congress on Obesity (ECO) in Malaga, Spain, evaluated SYNT-101 for safety, tolerance, and its effects on key hormones that control hunger and fullness. The early results are encouraging. Participants tolerated the treatment well, with no serious side effects, and showed signs of appetite control and metabolic benefits.

“These data validate the potential of SYNT-101 to induce metabolic changes that support glycemic control, weight loss and energy balance,” said Rahul Dhanda, chief executive officer of Syntis Bio, the Boston-based biopharmaceutical company developing SYNT-101.

“We believe that SYNT-101 will provide a convenient, more sustainable oral alternative and/or complement to systemic therapies such as GLP-1 drugs. The millions of people living with obesity need novel treatment options that are safe, effective and avoid the high costs and severe side effects that often accompany available treatment options.”

Many obesity medications, like GLP-1 receptor agonists, are effective in aiding weight loss, but loss of lean muscle remains a common concern. There are also ongoing issues with these drugs around accessibility, gastrointestinal side effects and long-term maintenance.

Mimicking Gastric Bypass with a Daily Pill

SYNT-101 mimics the effects of gastric bypass by forming a temporary polydopamine coating in the duodenum, shifting nutrient exposure to the lower intestine to naturally promote satiety and support metabolic balance.

In addition, this “duodenal nutrient exclusion” effect improves satiety and metabolic regulation, and has been shown to better preserve lean muscle mass compared to GLP-1 drugs. The polydopamine lining is designed work for up to 24 hours, after which it is naturally cleared from the body. SYNT-101 will ultimately be delivered in a once-daily oral pill.

In preclinical studies, SYNT-101 has shown promising effects on glycemic control and produced weight loss of 1% a week for six weeks while preserving 100% of lean muscle mass in rodent models.

In the human pilot study, nine healthy participants (2 male, 7 female, aged 24–53 years, BMI 19–29 kg/m²), received a single dose of SYNT-101 in liquid form, administered in three dose levels. Two participants were given 25% of the target dose, three received 50% and four received the full target dose.

Researchers conducted safety assessments and oral glucose tolerance tests to evaluate the tolerability and efficacy of SYNT-101, as well as endoscopic imaging to check whether the upper part of the small intestine was fully coated with the temporary polydopamine lining.

Blood tests were also conducted before and after treatment with SYNT-101 to assess the effects on satiety and metabolic hormone levels, including liver enzymes, leptin (a hormone that regulates appetite) and ghrelin (a hormone that causes hunger).

Strong Safety Profile and Encouraging Metabolic Signals

Endoscopic imaging confirmed that the polymer coating formed as expected across the upper small intestine, and tissue samples showed that SYNT-101 was safely eliminated within 24 hours of administration. No adverse or serious adverse events were reported in any dosage group.

During the 10 days following treatment, liver enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), and bilirubin, remained stable for each participant, consistent with normal liver functioning.

Additionally, gastrointestinal tolerance was excellent, with no changes noted in the Gastrointestinal Symptom Rating Scale (GSRS), and all participants reported an average pain rating of 0.

Importantly, glucose tolerance tests revealed delayed uptake of glucose following SYNT-101 treatment. At 30 and 60 minutes, glucose absorption was far lower than in untreated patients, by roughly 35% and 21%, respectively. This delay suggests that absorption occurs later in the intestine, as expected, rather than in the coated region of the duodenum.

Although the pilot study was not designed to measure weight loss, participants receiving a full dose of SYNT-101 also received blood tests, which showed elevated levels of leptin and lower levels of ghrelin, consistent with findings from preclinical in vivo models showing reduced food intake.

The authors note that larger trials are needed to fully assess the drug’s efficacy and safety. Syntis Bio plans to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) during the second half of 2025.

Dhanda added, “We are eager to replicate these data in our upcoming Phase 1 clinical trial and further explore the ability of SYNT-101 to produce sustainable, safe, effective weight loss by reducing fat, preserving lean muscle, and stimulating natural production of satiety hormones to prevent weight regain.”

Meeting: European Congress on Obesity (ECO2025)

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