Investigational endoscopic therapy maintains weight after GLP-1 discontinuation

A single duodenal mucosal resurfacing (DMR) procedure maintained weight loss for up to six months after adults with obesity stopped GLP-1 medications, according to a randomized trial that included a sham comparison.

“Nearly one in five adults report having taken a GLP-1 receptor agonist drug at some point, and the results can be dramatic. However, an estimated 60-70% of patients discontinue these drugs within the first year for a variety of reasons, including cost, side effects, or simply not wanting to stay on a medication long-term," said lead author Shelby Sullivan, MD, during a press briefing ahead of Digestive Disease Week® (DDW) 2026.

In an ongoing multicenter, randomized, double-blind, sham-controlled trial known as REMAIN-1, Dr. Sullivan and colleagues are evaluating whether DMR can help maintain weight loss achieved with tirzepatide. DMR is an investigational endoscopic procedure that uses hydrothermal ablation to remove the duodenal mucosa, an area linked to metabolic problems, with the goal of producing lasting metabolic benefits.

Dr. Sullivan reported findings from the midpoint cohort of the trial, which enrolled GLP-1-naive patients ages 21 to 70 without diabetes and with a body mass index of 30 to 45 kg/m². After a tirzepatide run-in, eligible patients who achieved at least 15% total body weight loss stopped the medication and were randomized in a 2:1 ratio to DMR or sham at least one week later. All patients received structured lifestyle counseling.

“Participants really could not tell if they had had the sham or the real procedure because they really don't have much in the way of symptoms after the procedure,” noted Dr. Sullivan of director of the Endoscopic Bariatric and Metabolic Program at Dartmouth Health Weight Center and professor of medicine, Dartmouth Geisel School of Medicine,

A total of 45 patients achieved the weight-loss threshold. Of these, 30 underwent DMR and 15 received a sham procedure. The groups were similar at baseline: the average age was 43, 80% were women, and 42% had prediabetes.

All trial participants lost about 40 pounds on GLP-1 therapy. However, six months after stopping the drug, patients in the sham control group gained back about 40% more weight compared with their counterparts in the DMR group. There was also a clear dose-response effect: the more ablations performed, the greater the weight loss. “Those who had a longer length of resurfacing regained just 7 pounds, maintaining more than 80% of their weight loss, while the sham control group regained about twice that amount,” Dr. Sullivan said. “Importantly, there were no definite or probable treatment emergent [or] serious adverse events related to the device or procedure.”

If the results are validated in the full REMAIN-1 trial, DMR “could fundamentally change how we think about GLP-1 therapy and potentially be approved for use in the US, providing an off-ramp for patients who either can't or don't want to be on these drugs long-term with a minimally invasive procedure to lock in the metabolic benefit," she noted.

Loren Laine, MD, a gastroenterologist at Yale University School of Medicine, who moderated the briefing, said he finds the research compelling, both clinically and in terms of how the body works. He noted that it highlights the duodenum’s key role in metabolic processes, including insulin resistance, diabetes, and obesity. “Interestingly, other studies have shown that injuring the duodenum or even bypassing the duodenum can impact metabolic function and weight,” Dr. Laine said.

According to Dr. Sullivan, the REMAIN-1 trial is now fully enrolled with more than 300 participants, and top-line results are expected in the fourth quarter of 2026.

She reported research support from Fractyl Health, Nitinotes Surgical, and Viking Therapeutics, as well as consulting relationships with Biolinq and Olympus (with prior roles at Allurion Technologies and Fractyl Health). She also disclosed holding stock in Biolinq. Her colleagues reported no disclosures.

DDW is AGA's annual meeting, jointly sponsored by AGA, AASLD, ASGE, and SSAT. Learn more at ddw.org.