An outpatient procedure may offer a way for an estimated 70 percent of people who stop popular weight-loss drugs to avoid regaining the pounds they’ve lost, according to a study to be presented at Digestive Disease Week.® (DDW) 2026. Nearly one in five adults with obesity have taken a glucagon-like peptide-1 (GLP-1), and many experience weight rebound once they stop the drug, regaining their lost weight within 18 months on average.
The study presents the first blinded, randomized, sham-controlled demonstration that the procedure known as duodenal mucosal can provide a safe, effective and durable way to maintain drug-free weight loss after stopping GLP-1.
As effective as GLP-1 drugs are, many people stop taking them because of cost, side effects, or simply because they don’t want to take a drug long-term. But if these drugs are stopped, weight regain occurs in the vast majority of patients and the metabolic benefits are lost. Finding a treatment that allows patients to stop these drugs without weight regain or loss of metabolic benefit is a huge unmet need. These findings suggest that this minimally invasive procedure may provide sustained weight loss maintenance.”
Shelby Sullivan, MD, lead author, director of the Endoscopic Bariatric and Metabolic Program at the Dartmouth Health Weight Center and professor of medicine, Dartmouth Geisel School of Medicine
Duodenal mucosal repair is an exploratory endoscopic procedure that uses targeted heat to remove (burn away) the unhealthy inner mucosal lining of the duodenum, the upper part of the small intestine just below the stomach. The REMAIN-1 trial is testing whether resurfacing of the duodenal mucosa, which stimulates the growth of new, healthy tissue, can lead to sustained metabolic recovery.
The findings are based on the first group of trial participants, who now have six months of follow-up data. Of the 45 participants in the average trial cohort, 29 underwent recurrence and 16 underwent a sham procedure. All participants underwent the procedure after losing at least 15% of total body weight using tirzepatide and then discontinuing the drug.
Patients lost approximately 40 kg on GLP-1 treatment. Six months after stopping the drug, those who had the sham procedure regained 40% more weight than the treatment group. What’s more, those who had more tissue reappear regained just 7 pounds, maintaining more than 80 percent of their weight loss, while the sham control group regained about twice that amount. The difference between the treatment and control groups appeared to widen from one to six months after the intervention, suggesting the potential for sustained weight maintenance with the procedure.
“What is particularly encouraging is that the benefit appears to increase over time rather than wane, and that it behaves like a drug in terms of dose response,” Dr. Sullivan said. “This gives us confidence that we are targeting the correct biology.”
No serious complications from either the device or the procedure were reported.
“Other than recovering from general anesthesia, there’s not a lot of recovery time,” Dr. Sullivan said. “You can go back to your daily routine in about a day. Participants couldn’t tell if they had the virtual or real procedure because there aren’t many symptoms after the procedure.”
The process focuses on the small intestine, where the hormones that mimic GLP-1 drugs are produced, Dr. Sullivan said. Over time, diets high in fat and sugar can lead to thickening and other changes in the lining of the duodenum. These changes rewire how the gut responds to food, affecting hormone production and leading to insulin resistance and metabolic disease. By revitalizing the mucosal layer, the resurfacing procedure aims to return individuals’ metabolism to their new post-GLP-1 weight, leading to sustained results.
Duodenal mucosal repair is an exploratory outpatient procedure. The more than 300-participant REMAIN-1 pivotal program, sponsored by Fractyl Health, is fully enrolled and randomized, with semiannual key cohort data expected in early Q4 2026 and a planned marketing submission later in the year.
