Fractyl Health Study Shows Revita Helps Prevent Weight Regain After Stopping Popular GLP-1 Drugs

Author: Benzinga Newsdesk | September 26, 2025 06:01am

Fractyl Health, Inc. (NASDAQ: GUTS) (the Company or Fractyl), a metabolic therapeutics company focused on pattern breaking approaches that treat root causes of obesity and type 2 diabetes (T2D), today announced groundbreaking results from the REMAIN-1 Midpoint Cohort, supporting the potential for Revita to be the first therapy to preserve weight loss after GLP-1 drug discontinuation. At 3 months, Revita-treated patients lost an additional 2.5% total body weight after stopping tirzepatide, while sham patients regained 10% (p=0.014). These results are clinically and statistically significant and provide randomized, blinded evidence that drug-free, durable weight maintenance is possible. They further support Revita as a potential first-in class treatment in a new therapeutic category in obesity care: post-GLP-1 weight maintenance.

"One of the biggest challenges in obesity medicine today is what happens when patients stop GLP-1 therapy, whether because of cost, insurance coverage, or side effects. We know weight regain almost always follows," said Shelby Sullivan, M.D., Professor of Medicine at the Geisel School of Medicine at Dartmouth University. "The REMAIN-1 3-month results are the first randomized, controlled evidence suggesting that a one-time endoscopic procedure may help maintain drug-free weight loss after GLP-1 discontinuation. The treatment difference we saw in this study, with Revita patients continuing to lose weight while sham patients rapidly regained weight, is striking. If these findings continue to hold with more data, duodenal mucosal resurfacing could represent a novel and much-needed solution to the largest gap in obesity care: post-GLP-1 weight maintenance."

REMAIN-1 Midpoint Cohort Study Design

The REMAIN-1 Midpoint Cohort (N=45) is a randomized, double-blind, sham-controlled study designed to evaluate Revita in adults with obesity who achieved at least 15% total body weight loss with tirzepatide. After discontinuing the drug, participants were randomized 2:1 to Revita or a sham endoscopic procedure. The key efficacy endpoint was total body weight change in Revita versus sham at 3 months.

The Midpoint Cohort is designed to be identical to the ongoing Pivotal Cohort, serving as an early readout to reinforce confidence in the pivotal program and provide initial validation of the study design and endpoints.

Key Findings

Data shared are for the treatment period of up to 3 months. The Midpoint Cohort is ongoing, with 6-month randomized data expected in Q1 2026.

• Clear evidence of Revita activity: The study met its 3-month efficacy endpoint with strong statistical significance (p=0.014), delivering 2.5% further weight loss with Revita (n=29) even after stopping tirzepatide, versus 10% weight regain in sham-treated patients (n=16).
• Excellent safety and tolerability through 3 months: No Revita-related SAEs or Grade II+ AEs were observed. Side effects were infrequent, mild, and transient, consistent with prior Revita clinical study experience.
• Positive readthrough to pivotal study: These data strengthen confidence in the ongoing Pivotal Cohort study, which is on track to complete randomization in early 2026, with 6-month topline primary endpoint data and potential PMA filing expected in H2 2026.
  
  "These results are a defining milestone for Fractyl and the obesity community. For the first time, randomized, blinded data show that Revita may dramatically prevent weight regain after GLP-1 discontinuation at 3 months. This is a compelling demonstration that targeting the gut may provide a remarkable and clinically significant improvement in obesity," said Harith Rajagopalan, M.D., Ph.D., Co-Founder and Chief Executive Officer of Fractyl Health. "The implications are profound. Patients want durable weight loss without the need for chronic medical therapy. The Revita clinical profile in this study suggests we have the potential to create a new standard of care in obesity with a disease-modifying intervention that allows us to progress from chasing weight loss to sustaining health with a durable metabolic reset."

Upcoming Milestones

The REMAIN-1 Midpoint Cohort is ongoing, with 6-month data expected in Q1 2026. The REMAIN-1 Pivotal Cohort has completed enrollment, and the Company remains on track to randomize patients in early 2026 and deliver 6-month topline primary endpoint data and potentially file a PMA in H2 2026. These milestones are designed to evaluate Revita as the first potential therapy for post-GLP-1 weight maintenance and to open a new therapeutic category in obesity care.

Posted In: GUTS