Promising Oral Obesity Treatment Mimics Gastric Bypass
An oral obesity treatment (SYNT-101) that mimics the metabolic effects of gastric bypass established preliminary safety, tolerability, and efficacy in a first-in-human study. METHODOLOGY: Researchers administered a single dose of the gastric bypass mimetic to nine healthy participants aged 24-53 years, with a body mass index ranging from 19 to 29; two participants received 25%, three received 50%, and four received 100% of the SYNT-101 target dose level.
Because SYNT-101 was designed to treat obesity by establishing a temporary polydopamine tissue lining to redirect nutrient absorption past the proximal to the distal bowel, endoscopic imaging was used to check whether the lining fully covered the upper part of the small intestine.
Plasma samples were collected before and after the treatment to evaluate the effects on satiety and metabolic hormone levels, including liver enzymes, leptin, and ghrelin.
Safety assessments and oral glucose tolerance tests were conducted to evaluate efficacy and tolerability. TAKEAWAY: Endoscopic imaging showed 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, with no adverse or serious adverse events reported in any dosage group.
During the 10 days following treatment, liver enzymes — including aspartate transaminase, alanine transaminase, and bilirubin — remained stable for each participant, consistent with normal liver functioning.
Gastrointestinal tolerance was 'excellent,' according to the authors, with no changes noted in the Gastrointestinal Symptom Rating Scale, and all participants reporting an average pain rating of 0.
Glucose tolerance tests showed delayed uptake of glucose following SYNT-101 treatment; at 30 and 60 minutes, glucose absorption was lower than that in untreated patients by roughly 35% and 21%, respectively, suggesting that absorption occurs later in the intestine, as expected, rather than in the coated region of the duodenum. IN PRACTICE:
'These data validate the potential of SYNT-101 to induce metabolic changes that support glycemic control, weight loss, and energy balance,' Rahul Dhanda, chief executive officer of Syntis Bio, the Boston-based biopharmaceutical company developing SYNT-101, said in an accompanying comment. 'We believe that SYNT-101 will provide a convenient, more sustainable oral alternative and/or complement to systemic therapies such as GLP-1 [glucagon-like peptide 1] drugs.' SOURCE:
The study was presented by Mary Ashley Hudson, PhD, Syntis Bio, at the European Congress on Obesity (ECO) 2025 in Málaga, Spain. LIMITATIONS:
This was a pilot study. Larger trials are needed to fully assess the drug's efficacy and safety. DISCLOSURES:
No funding information was provided. The authors declared having no competing interests.
Credit
Lead image: Jetsam86/Dreamstime
Medscape Medical News © 2025 WebMD, LLC
Cite this: Promising Oral Obesity Treatment Mimics Gastric Bypass - Medscape - May 16, 2025.
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