Fractyl Health (NASDAQ:GUTS) reported one-year data from the randomized midpoint cohort of its REMAIN-1 study, saying its Revita procedure helped patients maintain a larger share of GLP-1-induced weight loss after discontinuing GLP-1 therapy compared with a sham procedure.
On the company’s data call, Co-Founder and CEO Dr. Harith Rajagopalan said patients treated with Revita maintained “up to 84%” of their GLP-1-induced weight loss at one year, compared with 46% in the sham arm among patients who received complete duodenal ablations. He said the results address “the most significant unmet need in obesity today,” which he described as durable weight maintenance after stopping GLP-1 therapy.
One-Year Data Show Reduced Weight Regain
The REMAIN-1 midpoint cohort enrolled patients with obesity who had a body mass index between 30 and 45, were GLP-1 naive and did not have type 2 diabetes. Participants were started on tirzepatide and needed to achieve at least 15% total body weight loss before discontinuing GLP-1 therapy and being randomized two-to-one to Revita or sham.
Rajagopalan said the study was not formally powered for statistical significance and was intended to generate descriptive data to inform the pivotal trial. Forty-one of 45 randomized patients completed 52 weeks of follow-up, and the company said no participants restarted GLP-1 therapy after randomization.
According to Rajagopalan, Revita reduced weight regain by about 40% versus sham in the full modified intent-to-treat population. In patients who received complete ablations, the reduction in regain exceeded 60% versus sham. He said sham patients regained about 13% from nadir, or 54% of their GLP-1 weight loss, at one year.
In the complete ablation population, Rajagopalan said Revita patients retained 81% of their weight loss at one year, while sham patients retained less than half. In what the company called an “optimized population,” combining higher GLP-1 run-in weight loss and complete ablation, Revita patients regained 16% of their GLP-1 weight loss compared with 54% in the sham arm.
Safety Profile Remained Favorable
Fractyl reported no new device-related treatment-emergent adverse events between six and 12 months and no device-related serious adverse events in the study. Rajagopalan said there were four mild treatment-emergent adverse events in total across two patients: abdominal discomfort, sore throat, nausea and dry mouth. He said all resolved within two days.
Rajagopalan also noted there were no new diagnoses of type 2 diabetes in the Revita arm, while one diagnosis occurred in the sham arm.
UCLA Investigator Cites Potential Clinical Demand
Dr. Adarsh Thakker, co-lead of the UCLA Bariatric Endoscopy Program, a REMAIN-1 investigator and a clinical adviser to Fractyl, said he was “highly enthusiastic” about the data. He said the separation between treatment groups appeared meaningful and sustained, adding that one concern had been whether Revita was only delaying weight regain rather than producing durable separation.
“As we start to see the curves get to their 1-year mark and beyond, we are starting to see hints of a plateau,” Thakker said, while noting the small size of the pilot study.
Thakker said he would describe the result to patients as keeping “an extra 15 pounds off compared to just stopping the GLP-1 agent,” based on the example presented by the company. He also said the safety profile was consistent with his clinical experience and suggested the procedure could be attractive to patients seeking to stop chronic medication.
Pivotal Trial and Regulatory Timeline
Rajagopalan said the ongoing REMAIN-1 pivotal study has the same design, patient population, enrollment criteria, investigators and protocol as the midpoint cohort, calling it “a larger, well-powered version” of the same experiment. He said the company expects top-line six-month pivotal data in early fourth quarter 2026 and a potential FDA De Novo submission later in the same quarter.
In response to an analyst question, Rajagopalan said the company expects the FDA will want to review available 12-month data as part of the regulatory process. He said Fractyl has received favorable feedback on the De Novo pathway, while adding that final decisions would depend on the FDA’s review of safety data in the submission.
During the question-and-answer session, Rajagopalan also said dropouts in the pivotal trial will be handled through a mixed model for repeated measures analysis, with missing data treated as missing at random. He said the trial includes a centralized diet and lifestyle program, consisting of a 500-calorie deficit and weekly exercise recommendation, similar to GLP-1 studies.
Fractyl said it plans to hold an investor day later in the quarter to discuss the commercial opportunity and market access strategy for Revita. Rajagopalan said the company remains funded through the pivotal data expected later this year.
About Fractyl Health (NASDAQ:GUTS)
Fractyl Health, Inc is a clinical-stage medical technology company focused on the development and commercialization of minimally invasive, endoscopic therapies for metabolic diseases. Headquartered in Lexington, Massachusetts, Fractyl is advancing treatments that target the underlying physiology of conditions such as type 2 diabetes, obesity and nonalcoholic fatty liver disease (NAFLD) by modifying the duodenal mucosa to improve metabolic control.
The company’s lead product, Revita® Duodenal Mucosal Resurfacing (Revita DMR), employs a catheter-based hydrothermal ablation technique to remodel the lining of the upper small intestine.
