Fractyl Health (NASDAQ:GUTS) presented prospective, randomized, double-blind, controlled six-month data from its REMAIN-1 midpoint cohort pilot study, highlighting results the company said support Revita’s ability to help patients maintain weight loss after discontinuing GLP-1 therapy. Management also discussed regulatory interactions with the U.S. Food and Drug Administration (FDA), the enrollment status and endpoints of the ongoing pivotal trial, and early commercial preparation activities focused on reimbursement pathways.
Six-month midpoint cohort data: weight regain attenuated versus sham
Chief Executive Officer and co-founder Dr. Harith Rajagopalan said the REMAIN-1 midpoint cohort showed “sustained weight maintenance with excellent safety and tolerability” six months after patients stopped tirzepatide. The study enrolled 45 adults with obesity without type 2 diabetes who were GLP-1 naïve, started on tirzepatide, and titrated until they achieved at least 15% total body weight loss. Tirzepatide was then discontinued and participants were randomized 2-to-1 to Revita versus sham.
Fractyl reported that, at six months after tirzepatide discontinuation, Revita-treated patients regained an average of 4.5% of body weight versus 7.5% in the sham arm in the full efficacy population, with a one-sided p-value of 0.07. Rajagopalan said approximately 30% of Revita-treated patients either maintained their weight loss or continued to lose weight through six months.
Management emphasized that the pilot was initially designed as a three-month study and “was not powered formally for hypothesis testing,” adding that p-values were presented to describe the “strength and consistency” of the observed effect.
Subgroup analysis: larger effect in patients with greater GLP-1 run-in weight loss
Rajagopalan highlighted an analysis examining outcomes based on the magnitude of GLP-1–induced weight loss during the run-in period, noting that patients who lose more weight on GLP-1 therapy are often at higher risk of rapid regain when drugs are stopped. In patients with above-average GLP-1–induced weight loss in REMAIN-1, Fractyl reported Revita reduced post-GLP-1 weight regain by approximately 70% versus sham at six months, with a p-value of 0.004.
In absolute terms, Fractyl said sham patients in that subgroup regained about 13% of body weight over six months, compared to about 4% for Revita-treated patients. The company described this as a “biologically coherent enrichment signal” and said it reinforced confidence in the pivotal study design.
Other endpoints: lipid markers and patient-reported sweet cravings
Fractyl also discussed secondary and exploratory endpoints that it said were consistent with prior observations about Revita’s metabolic effects. At six months, the company reported improvements versus sham in:
- HDL cholesterol (p=0.01)
- Triglyceride-to-HDL ratio (p=0.03)
On patient-reported outcomes, Fractyl said Revita-treated patients reported significantly reduced craving for sweet foods compared to sham (p=0.04). Rajagopalan characterized sweet craving as an early driver of post-GLP-1 rebound and said the finding was consistent with Revita’s proposed gut-brain mechanism.
Site variability noted; pivotal study fully enrolled and nearing final randomization
Rajagopalan addressed variability observed at one site, where both Revita and sham arms saw increased weight gain. He said the company identified the issue through central statistical monitoring and noted that the site “is not contributing materially to the pivotal cohort,” though it contributed meaningfully to the pilot. He added that when excluding that site, the treatment difference between Revita and sham expanded between month three and month six.
On the ongoing pivotal study, Rajagopalan said it is fully enrolled, with approximately 95% of participants randomized. The company expects to complete randomization in February and remains on track for top-line pivotal data and a potential FDA filing in the second half of 2026. He said the pivotal study will assess percent weight regain at six months and responder rate at 12 months.
During Q&A, management said it expects to see a 50% reduction in weight regain for Revita versus sham in the pivotal study, based in part on higher run-in weight loss in the pivotal cohort compared with the pilot. The company also said non-adherence exclusions in the pilot were pre-specified; five patients were excluded from the six-month efficacy analysis due to successive non-adherence to diet and lifestyle recommendations over at least three visits. Management added the pivotal study will include sensitivity analyses evaluating that population.
Regulatory discussions: De Novo reclassification request and upcoming FDA feedback
Fractyl said it has had “constructive and interactive” discussions with the FDA regarding Revita’s safety and tolerability, and it requested FDA feedback on reclassifying Revita under the De Novo pathway rather than the PMA pathway. The company said it expects FDA feedback in the second quarter of 2026.
In Q&A, Rajagopalan described the regulatory milestones he said the FDA is looking for in the pivotal program: statistical significance (p<0.05, two-sided) at six months for the co-primary endpoint, and at least 50% of Revita patients maintaining at least 5% of the weight they lost on tirzepatide at one year. He said the company believes it is “incredibly well on track” for those milestones.
Looking ahead, management reiterated plans to advance commercial readiness efforts, including reimbursement-focused activities tied to its Breakthrough Device Designation and the CMS Transitional Pass-Through pathway. The company also outlined expected catalysts including completing pivotal randomization in February, FDA feedback on De Novo in Q2 2026, one-year data from the REVEAL-1 cohort in Q2, one-year randomized REMAIN-1 data in Q3, and six-month primary endpoint data and a potential FDA filing in the second half of 2026.
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.
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