An investigational endoscopic procedure may help patients maintain weight loss after stopping tirzepatide, interim trial results suggest, with the benefit appearing to grow over time rather than diminish.
Interim results from the REMAIN-1 trial, presented at Digestive Disease Week (DDW) 2026, showed patients who underwent duodenal mucosal resurfacing (DMR) after discontinuing tirzepatide regained significantly less weight than those who received a sham procedure.
In the first 45 patients with six months of follow-up, those in the sham arm regained 40% more weight than those who received DMR, after both groups had lost around 18 kg each on tirzepatide.
At three months, the sham arm had regained 8.2±3.5 kg compared with an additional loss of 2.1±2.2 kg in the DMR group, a treatment difference of 10.3 kg (p=0.014). The gap between the groups appeared to widen from one to six months post-procedure, raising the possibility of durable benefit.
Principal investigator Dr Shelby Sullivan, director of the Endoscopic Bariatric and Metabolic Program at Dartmouth Health Weight Center in the US, said the findings addressed a significant gap in care.
“Finding a treatment that allows patients to stop these medications without weight regain or loss of metabolic benefit is a huge unmet need. These findings indicate that this minimally invasive procedure may provide lasting weight-loss maintenance,” she said.
Many patients stopped GLP-1RAs because of cost, side effects, or a preference to avoid long-term medication use, Dr Sullivan said. If approved, DMR could provide an “off ramp” that allowed shorter or reduced reliance on these drugs.
Dr Sullivan said the procedure aimed to reset metabolism by ablating and regenerating the mucosal lining of the duodenum, a site she described as central to metabolic dysfunction. She said high-fat, high-sugar diets could thicken this layer, reducing enteroendocrine cell activity and increasing absorptive capacity in patients with obesity.
“When we do this procedure, we’re essentially ablating the top layer of mucosa, so that it grows back normal. We get a small amount of weight loss with this therapy by itself, significant improvement in metabolic function, improvement in glucose control and improvement in hepatic steatosis and MASH,” she said.
Dr Sullivan hypothesised that changes in hunger signalling following the metabolic reset may help explain the procedure’s durability.
No serious complications related to the device or procedure were reported.
The double-blind, multicentre pivotal trial, sponsored by metabolic therapeutics company Fractyl Health, is ongoing. Final results will be based on data from 300 participants. The baseline cohort had a BMI of 30–45 kg/m² and no diabetes.