Patients treated with duodenal mucosal resurfacing (DMR), an investigational endoscopic procedure, showed notable reductions in weight regain after discontinuing the weight-loss drug tirzepatide, according to 6-month results from the ongoing REMAIN-1 trial.
“If validated in the full trial, this procedure could fundamentally change how we think about GLP-1 therapy, and potentially be approved for use in the US,” said first author Shelby Sullivan, MD, in a briefing for the study, being presented at Digestive Disease Week (DDW) 2026.
The intervention could “provide 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,” said Sullivan, who is director of the Endoscopic Bariatric and Metabolic Program at Dartmouth Health Weight Center, Hanover, New Hampshire.
Despite the widespread popularity of GLP-1 drugs for weight loss, real-world studies suggest that an estimated 70% of patients discontinue the drugs, after which weight regain can be rapid and substantial, highlighting the need for interventions post-discontinuation.
DMR, a minimally invasive procedure performed on an outpatient basis, uses hydrothermal ablation to remove the unhealthy inner mucosal lining from the duodenum, which can thicken over time and play a role in metabolic dysfunction.
The resurfacing procedure is theorized to trigger a “metabolic reset,” potentially “reducing reliance on chronic pharmacotherapy and preventing post-withdrawal weight regain,” Sullivan explained.
The intervention has been evaluated for various indications, and shows benefit in the treatment of insulin-treated type 2 diabetes and conditions including hepatic steatosis in metabolic dysfunction-associated steatohepatitis (MASH).
REMAIN-1 Program
To test the approach in post-tirzepatide weight changes, Sullivan and her colleagues are conducting an ongoing multicenter, double-blind, sham controlled pivotal trial of more than 300 patients with obesity who achieved at least 15% of total body weight loss through treatment with the dual GLP-1/ GIP receptor agonist tirzepatide.
This arm of the program follows promising results from an open-label arm of 15 patients who were all treated with DMR following discontinuation of tirzepatide who were followed for 3 months, as previously reported by Medscape Medical News.
The participants in the current study were randomized 2:1 at least 1-week post-discontinuation to receive either the resurfacing treatment or a sham procedure.
Of note, patients in both groups were intubated and had an endoscope taken down to the small bowel, where only the treatment group received the actual ablation.
A total of 80% of the participants were female, 42% had prediabetes, and their total body weight loss was 18 kg.
In reporting the first results from the midpoint pilot study, Sullivan described the results up to 6 months of 45 participants, including 29 who underwent resurfacing and 16 who received the sham procedure.
The patients had lost, on average, approximately 40 lbs while on tirzepatide.
At 6 months following drug discontinuation, the treatment group regained about 7 lbs, representing a 40% lower total body weight change vs the sham group (4.5% vs 7.5%; P = .07).
Patients in the treatment group who had more tissue resurfaced maintained more than 80% of their pre-discontinuation weight loss.
Safety?
Importantly, no serious complications were reported from either the resurfacing device or the procedure.
“Other than recovering from the general anesthesia, there isn’t much recovery time involved,” Sullivan said in a press statement. “You can be back to your daily routine in about a day.”
Despite both groups in the study receiving the intubation and endoscopic placement, “the symptoms are subtle enough that study participants could not tell if they had the sham or the procedure,” she added.
How It Works
The small bowel, targeted in the resurfacing procedure, is where hormones that are mimicked by GLP-1 drugs are produced. Changes over time in the duodenal mucosal layer specifically have effects on how the gut responds to food, including hormone production, potentially resulting in insulin resistance and metabolic disease, Sullivan explained.
“What we think is happening, based more on data from animal and human studies, is that there’s this transition to a more absorptive state,” she said.
“We’re essentially ablating the top layer of mucosa so that it grows back normally,” she added.
Regarding the key question of how long the results may last before another resurfacing is necessary, Sullivan noted that data from other studies suggests general stability for up to 2 years.
“My suspicion is that it’s at least going to last for 2 years, and probably a little bit longer than that, but we don’t have clear answers to that at this point,” she said at the press briefing.
Previous studies looking at various other indications have shown significant improvement in areas such as metabolic function, control of glucose and A1c, and even in hepatic steatosis in MASH.
While the resurfacing procedure has not shown significant effects as a weight loss tool on its own in diabetes, Sullivan noted that its effects in maintaining weight appear more promising. “Part of the reason why this is effective is because it is changing people’s hunger,” she said.
“Whether or not it’s changing food choices is a question that we need to delve into further, but it is still reducing overall food intake and hunger.”
Benefits Could Be ‘Significant’
In terms of potential reimbursement for the resurfacing procedure, Sullivan noted that a variety of avenues should be possible.
Commenting on the issue in the session, moderator Loren Laine, MD, who is chair of the DDW meeting, agreed that — with GLP-1 discontinuation rates known to be notably high — the benefits of an intervention to prevent the inevitable regaining of weight could be significant.
“In general, people aren’t good at taking medications, and frankly if a certain number of people stop them, the quality of life worsens and the costs increase as weight is regained, so I think it’s important,” said Laine, who is a professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine, New Haven, Connecticut.
Further commenting to Medscape Medical News, Laine noted that high interest will be on what future results show regarding the intervention’s durability and how long the differences in the regaining of weight are sustained.
“Slowing weight regain is a positive outcome, but it’s uncertain if patients and providers will view it as sufficient if patients do regain much or all of their weight over time,” he said.
Furthermore, “the authors also suggested that a greater length of ablation may have better efficacy, so exploring aspects of the ablation procedure in an attempt to optimize the procedure and outcomes will be useful,” he added.
Sullivan’s disclosures include consulting and/or relationships with Fractyl Health, Biolinq, and Olympus. Laine had no disclosures relating to the study.
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