For an estimated 70% of people who stop taking popular weight loss drugs, outpatient surgery may be a way to avoid regaining lost weight, according to study results to be presented at Digestive Disease Week® (DDW) 2026. Nearly 1 in 5 obese adults take glucagon-like peptide-1 (GLP-1), and many experience weight rebound after stopping the drug, regaining weight loss within an average of 18 months.
This study presents the first blinded, randomized, sham-controlled evidence that a procedure known as duodenal mucosal resurfacing may provide a safe, effective and durable method to maintain weight loss without drugs after GLP-1 discontinuation.
Although GLP-1 drugs are effective, many people stop taking them because of cost, side effects, or simply because they don’t want to take them long-term. However, when these drugs are discontinued, the majority of patients regain weight and lose their metabolic benefits. Finding treatments that allow patients to discontinue these drugs without weight regain or loss of metabolic effects is a major unmet need. These findings indicate that this minimally invasive procedure may enable sustained weight loss maintenance. ”
Shelby Sullivan, MD, first author, director of the Endoscopic Obesity and Metabolism Program at the Dartmouth Healthy Weight Center and professor at the Dartmouth Geisel School of Medicine
Duodenal mucosal resurfacing is an investigational endoscopic surgery that uses targeted heat to remove (cauterize) the unhealthy inner mucosal layer of the duodenum, the upper part of the small intestine just below the stomach. The REMAIN-1 trial is testing whether resurfacing the duodenal mucosa, which stimulates the growth of new healthy tissue, results in a sustained metabolic reset.
The findings are based on the first group of trial participants, with six months of follow-up data now available. Of the 45 participants in the trial’s midpoint cohort, 29 received resurfacing and 16 received a sham procedure. All participants received treatment after losing at least 15% of their total body weight using tirzepatide and then discontinuing the drug.
With GLP-1 therapy, the patient lost approximately 40 pounds. Six months after stopping the drug, the sham group regained 40% more weight than the treatment group. Additionally, the group that had more tissue resurfaced regained just 7 pounds and maintained more than 80 percent of the weight they lost, while the sham control group regained about twice that. Differences between the treatment and control groups appeared to widen from 1 to 6 months after the intervention, suggesting that this procedure may result in sustained weight maintenance.
“What’s particularly encouraging is that its effects appear to increase rather than wane over time, and it acts like a drug in terms of a dose response,” Dr. Sullivan said. “This gives us confidence that we are targeting the right biology.”
No serious complications were reported from either the device or the procedure.
“Other than recovering from general anesthesia, recovery doesn’t take long,” Dr. Sullivan says. “People can return to their daily activities in about a day. Participants didn’t know whether they had a fake or real surgery because they didn’t have many symptoms after the surgery.”
The procedure focuses on the small intestine, where hormones mimicked by GLP-1 drugs are produced, Dr. Sullivan said. A high-fat, high-sugar diet can cause thickening and other changes in the duodenal mucosal layer over time. These changes rewire how the gut responds to food, affect hormone production, and lead to insulin resistance and metabolic disease. By rejuvenating the mucosal layer, this resurfacing procedure aims to reset an individual’s metabolism to their new post-GLP-1 weight and provide lasting effects.
Duodenal mucosal resurfacing is an investigational outpatient surgical therapy. The pivotal REMAIN-1 program, sponsored by Fractyl Health and involving more than 300 participants, is fully enrolled and randomized, with topline six-month critical cohort data to be released in early Q4 2026, with marketing submission expected later that year.
