Fractyl Health Reports Positive Randomized Data from REMAIN-1 Midpoint Cohort Demonstrating Durable Weight Maintenance One Year After GLP-1 Discontinuation (Form 8-K)

Fractyl Health Reports Positive Randomized Data from REMAIN-1 Midpoint Cohort Demonstrating Durable Weight Maintenance One Year After GLP-1 Discontinuation

Up to 84% of GLP-1 induced weight loss retained with Revita® versus 46% with sham at one year in patients receiving complete duodenal ablations

Next anticipated Revita® milestones are topline six-month randomized data from the REMAIN-1 Pivotal Cohort in early Q4 2026 and a potential FDA De Novo marketing application submission in late Q4 2026

Company to host investor webcast today at 8:00 a.m. ET

BURLINGTON, Mass., July 15, 2026 (GLOBE NEWSWIRE) - Fractyl Health, Inc. (Nasdaq: GUTS) (the Company or Fractyl), a clinical-stage metabolic therapeutics company focused on pioneering novel approaches to treat obesity and type 2 diabetes (T2D), today announced positive one-year results from its REMAIN-1 Midpoint Cohort ("Midpoint Cohort"). The new results reinforce the potential of the Revita DMR System (Revita) to be the first durable procedural therapy for post-GLP-1 weight maintenance.

Key Findings:

Figure 1: Change in body weight in (i) Complete Ablation population: > 14 cm duodenal ablation, no run-in weight loss restriction (Sham n=16, Revita n=17) and (ii) Optimized population: complete ablation (> 14 cm) and run-in weight loss ≥ 17.5% (Sham n=8, Revita n=10). Y-axis: LS-mean % total body-weight change from baseline; MMRM, compound-symmetry covariance, estimated at 20% run-in weight loss; error bars ± SE; n contributing shown per visit below axis. Retention = % of run-in weight loss maintained at 12 months. Exploratory REMAIN-1 Midpoint Cohort subgroup; not powered for formal inference. Abbreviations: MMRM, mixed-model repeated measures; LS-mean, least-squares mean; SE, standard error.

"The success of GLP-1 medicines has created a new unsolved problem: what happens when patients stop. Most do stop eventually, whether because of cost, side effects, or simply not wanting to inject a drug for the rest of their lives. When they stop, the weight most often comes back," said Harith Rajagopalan, M.D., Ph.D., Co-Founder and Chief Executive Officer of Fractyl. "Today's results are the first randomized, sham-controlled evidence that a single Revita procedure can keep most of the weight off for a full year after GLP-1 is stopped, without the need for ongoing medication. We eagerly anticipate an early Q4 2026 topline readout from the REMAIN-1 Pivotal Cohort with deep conviction that Revita may represent the first procedural entrant into the post-GLP-1 weight maintenance category."

Webcast

Fractyl Health will host a webcast today, July 15, 2026, at 8:00 a.m. Eastern Time. The live webcast can be accessed by clicking this link. This webcast can also be found in the "Events" section of Fractyl's website at ir.fractyl.com. The webcast will be archived and available for replay for at least 30 days after the event.

About REMAIN-1 Weight Maintenance Program

REMAIN-1 is Fractyl Health's pivotal program evaluating Revita for weight maintenance in adults with obesity following discontinuation of GLP-1 therapy. The Midpoint Cohort (N=45) is a randomized, double-blind, sham-controlled study in adults who achieved at least 15% total body weight loss on tirzepatide; after discontinuing the drug, participants were randomized 2:1 to a single Revita procedure or a sham endoscopic procedure and followed for one year. The Midpoint Cohort is not powered for formal statistical significance; results are descriptive and are intended to characterize the treatment effect and inform the Pivotal Cohort design and execution. Results in the Midpoint Cohort at one year are evaluated per the pre-specified statistical analysis plan defined for the pivotal study, with GLP-1 weight loss fitted as a

covariate on treatment effects, calculated as least-square means at the 20% reference. Both a Complete Ablation cohort (defined as >14cm of duodenal ablation) and an Optimized responder population (with > 14 cm duodenal ablation and ≥17.5% run-in weight loss) are pre-specified key secondary endpoints in the pivotal study. The Pivotal Cohort is fully randomized and well powered at the expected effect size to clear both co-primary endpoints in the modified intention-to-treat (mITT) population: (i) weight regain at six months (Revita versus sham) and (ii) a responder rate defined as the proportion of participants maintaining at least 5% total body weight loss relative to their pre-tirzepatide weight at one year. Topline six-month randomized data from the Pivotal Cohort are anticipated in early Q4 2026.

About Revita

Revita is Fractyl Health's lead product candidate, designed to remodel the duodenal lining via a one-time, minimally invasive endoscopic procedure intended to restore healthy nutrient sensing and signaling disrupted by chronic metabolic disease. Revita has received Breakthrough Device designation from the FDA for weight maintenance in people with obesity who discontinue GLP-1 therapies. Revita is for investigational use only in the United States and is CE marked in the European Union and United Kingdom.

About Fractyl Health

Fractyl Health is a clinical-stage metabolic therapeutics company advancing two differentiated candidates designed to target the root causes of obesity and T2D: Revita, a procedural therapy in pivotal development for post-GLP-1 weight maintenance, and Rejuva, an AAV-based gene therapy platform with its lead candidate RJVA-001 entering first-in-human clinical studies. Fractyl's goal is to advance metabolic disease treatment from chronic management toward prevention and reversal of disease. Fractyl is headquartered in Burlington, Massachusetts.