Fractyl Health (NASDAQ:GUTS) reported six-month top-line results from its ongoing pivotal REMAIN-1 study evaluating its investigational Revita procedure for maintaining weight loss after patients discontinue GLP-1 obesity medicines.
The randomized, double-blind, sham-controlled study enrolled adults with obesity who had not previously received GLP-1 treatment. Participants first received tirzepatide during a run-in period, losing an average of 18.3% of body weight over an average 25 weeks, before discontinuing the medication and being randomized two-to-one to receive Revita or a sham procedure.
Six-Month Weight-Maintenance Results
Fractyl said Revita met the first of two co-primary endpoints at six months. In the modified intention-to-treat population of 308 randomized U.S. participants, patients in the Revita arm retained 80% of their GLP-1-induced weight loss, compared with 67% in the sham arm. The company reported a p-value of 0.0023 for the difference.
According to Co-Founder and CEO Harith Rajagopalan, nearly one-third of Revita-treated patients either maintained their GLP-1-associated weight loss or lost additional weight after stopping tirzepatide. About half retained at least 80% of their prior weight loss, the company said.
Rajagopalan said the separation between Revita and sham increased between month one and month six. However, the study’s second co-primary endpoint, which will assess Revita patients at 12 months, has not yet been evaluated. The company expects to report those results in the first quarter of 2027.
The 12-month endpoint will assess whether at least half of Revita-treated patients remain at least 5% below their body weight before beginning tirzepatide. Fractyl said its six-month model estimated a 97.2% responder rate using that methodology, though the company has not yet determined the 12-month outcome.
Ablation Length and Safety Findings
Revita is an endoscopic procedure designed to ablate the duodenal mucosa. Fractyl reported that greater ablation lengths were associated with less weight regain. Patients receiving at least 12 centimeters of treatment had 43% less weight regain than the sham group, while those receiving more complete treatment of the duodenum had 53% less regain than sham, according to the company.
Rajagopalan said the longer-treatment findings were consistent with prior pilot work and could inform future physician training if the procedure receives regulatory clearance. The company plans to formally evaluate certain ablation-length analyses after the 12-month co-primary endpoint is assessed.
Fractyl reported no device- or procedure-related serious adverse events through six months. Two Revita participants and four sham participants experienced serious treatment-emergent events, none of which was adjudicated as probably or definitely related to the device or procedure, the company said. Procedure-related events were predominantly mild and generally occurred within seven days, with reported common events including throat pain, nausea and abdominal pain.
Patient retention was 94% through the six-month visit. Fractyl also said sham participants were three times more likely to restart anti-obesity medication than Revita participants. Under the study’s prespecified analysis plan, data following a restart of GLP-1 or other anti-obesity medication are censored, with the patient’s last weight before resumption used in the efficacy estimate.
Regulatory and Reimbursement Plans
Revita remains investigational in the United States. The company said the device has FDA Breakthrough Device Designation for post-GLP-1 weight maintenance and could potentially pursue a Class II De Novo regulatory pathway. Rajagopalan said Fractyl expects the FDA review clock to begin after it reports success on the second co-primary endpoint, anticipated in the first quarter of 2027, rather than before the 12-month data are available.
Fractyl said it is preparing for a potential De Novo submission later this year, while acknowledging that final regulatory authorization is not assured.
The company also highlighted recent coding and coverage developments. The American Medical Association published Category III CPT code 1122T for the Revita procedure, effective Jan. 1, 2027. Fractyl said it may also be eligible for CMS Transitional Pass-Through payment for Breakthrough Devices, subject to applicable requirements.
In addition, the company pointed to the CMS and FDA Regulatory Alignment for Predictable and Immediate Device coverage pathway, or RAPID, as a possible route to expedited coverage. Fractyl said the pathway remains subject to CMS policy development and that its potential applicability to Revita is uncertain.
Clinical Perspective
Adrian Dan, medical director of the Weight Management Institute at Summa Health, said the findings exceeded his expectations and could appeal to patients seeking an alternative to indefinite medication use or anatomy-altering surgery.
“Patients are looking for something durable,” Dan said. “They are looking for something minimally invasive, incisionless, and effective.”
Dan said the procedure’s safety profile and the relationship between ablation length and results could support adoption in metabolic and endoscopy practices if Revita is cleared. He estimated that a large metabolic center could initially perform 50 to 100 procedures per month with coverage, potentially increasing over time.
About Fractyl Health (NASDAQ:GUTS)
Fractyl Health, Inc is a clinical-stage biotechnology company focused on developing therapies for metabolic diseases, including type 2 diabetes and obesity. The company’s approach is based on targeting the biology of the gastrointestinal system and developing treatments intended to address underlying disease mechanisms rather than relying solely on chronic medication.
Fractyl Health’s lead product candidate is Revita, an investigational, minimally invasive endoscopic procedure designed to resurface the duodenal lining.
