A simple procedure that ‘resets’ the gut could help patients stop blockbuster GLP-1 weight-loss drugs without piling the pounds back on, researchers say.
In a new trial, people who underwent the treatment after losing at least 15 per cent of their body weight on tirzepatide regained far less weight than those given a sham procedure.
The findings could offer hope to millions taking obesity jabs such as Mounjaro and Zepbound who fear rapid weight rebound when they come off the medication.
One in five American adults has taken a GLP-1 medication for obesity, according to recent polling, with some losing up to 20 per cent of their body weight.
But recent research suggests most users regain much of the lost weight within two years of stopping treatment.
To combat this, experts at Dartmouth Geisel School of Medicine in New Hampshire tested a minimally invasive procedure known as duodenal mucosal resurfacing, or DMR.
The treatment is carried out under general anaesthetic as an outpatient procedure.
Doctors pass a thin flexible tube through the mouth, down the stomach and into the duodenum – the first part of the small intestine.
In a study, people who lost at least 15 percent of their body weight on tirzepatide and then quit lost an additional four pounds over three months after getting the DMR procedure (stock)
Once in place, a heated balloon is used to remove part of the gut lining.
New tissue then grows back, which researchers believe may help restore metabolic function and alter hormones involved in hunger and blood sugar control.
The duodenum helps produce hormones that regulate hunger, fullness and blood sugar – the same appetite pathways targeted by drugs such as Ozempic and Mounjaro.
But researchers believe years of eating fatty, sugary foods may damage and thicken the lining of this part of the gut, disrupting those signals and contributing to weight gain and poor metabolic health.
The procedure removes the old lining so a healthier one can grow back.
The small study enrolled 46 adults with obesity who had never taken a GLP-1 drug before the trial began.
They first took tirzepatide – sold under the brand names Mounjaro and Zepbound – and lost 15 per cent of their starting body weight, or around 40lbs on average.
After stopping the drug, they were randomly assigned to either the real DMR procedure or a sham version.
At three months, DMR patients lost another 4.6 pounds, compared to an 18 pound regain in the sham group, a 22.7 pound difference favoring the procedure
Neither participants nor researchers knew who had received which treatment.
Over the following three months, those who had DMR lost a further four pounds on average.
Those in the sham group regained nearly 18 pounds.
After six months, people who received the fake procedure had regained 40 per cent more weight than those who underwent the real treatment.
Patients who had a larger area of intestinal lining treated performed best, regaining just seven pounds on average and maintaining more than 80 per cent of their original weight loss.
The sham group regained around 14 pounds.
Lead author Dr Shelby Sullivan, director of the Endoscopic Bariatric and Metabolic Program at Dartmouth Health Weight Center, said: ‘Finding a treatment that allows patients to stop these medications without weight regain or loss of metabolic benefit is a huge unmet need.’
She added: ‘What’s particularly encouraging is that the benefit appears to increase over time rather than fade, and that it behaves like a drug in terms of dose response. That gives us confidence that we’re targeting the right biology.’
Sixty to 80 percent of patients regain their lost weight within a year after stopping GLP-1 medications
No serious side effects related to the device or procedure were reported.
The study will be presented at Digestive Disease Week 2026.
Dr Sullivan added: ‘Other than recovering from the general anaesthesia, there isn’t much recovery time involved. You can be back to your daily routine in about a day.
‘Participants could not tell if they had the sham or real procedure because there are not a lot of symptoms after the procedure.’
Experts said the approach could eventually offer an alternative for patients who cannot tolerate GLP-1 drugs, struggle with the cost, or do not want to stay on injections indefinitely.
However, larger and longer-term studies will be needed before the procedure can be widely adopted.
