Slimming down on a GLP-1 is one thing — keeping the pounds off after stopping the drug is another.
But now, a groundbreaking new study suggests an experimental outpatient procedure may help prevent weight regain in patients no longer using the blockbuster diabetes and obesity meds.
“As effective as GLP-1 medications are, many people stop taking them because of cost, side effects or simply not wanting to take a drug long-term,” said Dr. Shelby Sullivan, lead author and director of the Endoscopic Bariatric and Metabolic Program at Dartmouth Health Weight Center.
Across the country, about 1 in 8 Americans have used GLP-1s for weight loss — but more than three-quarters quit taking them within two years.
And when they do, the results often reverse quickly.
One study found that people return to their pre-treatment weight within about a year and a half after stopping treatment, while another showed weight is regained about four times faster after discontinuing GLP-1s than after diet or exercise programs.
“We are facing a huge problem of weight regain after stopping GLP-1 medications,” Sullivan told The Post, describing it as an “urgent unmet medical need.”
“Durable weight loss maintenance is the holy grail of obesity treatment,” she added.
Now, Sullivan and her team believe they may be one step closer to it.
In the study, researchers enrolled 45 patients who had lost about 15% of their body weight — roughly 40 pounds — using tirzepatide, the active ingredient in GLP-1 drugs like Mounjaro and Zepbound, before stopping treatment.
Participants were split into two groups: 26 received an experimental procedure called duodenal mucosal resurfacing (DMR), while the rest underwent a sham procedure for comparison.
During the minimally invasive procedure, doctors guide a flexible camera known as an endoscope through the mouth, down the esophagus and into the stomach and duodenum — the upper part of the small intestine. Once in place, they use targeted heat to gently burn the inner lining.
The researchers chose to target the duodenum because it’s where key gut hormones are produced that GLP-1 drugs mimic to help control appetite, curb cravings and regulate blood sugar.
“Normally, the duodenum has different cell types to sense food, absorb nutrients and send signals to the liver, the pancreas and the brain,” Sullivan said. “However, with duodenum dysfunction, the sensing and signaling mechanisms are disrupted.”
She noted that this dysfunction is often linked to long-term high-fat, high-sugar diets, which can change the gut lining over time.
“We believe that DMR restores normal function of the duodenum,” Sullivan said, explaining that the goal is to essentially “reset” the gut’s metabolic signaling after weight loss.
Preliminary results, set to be presented at Digestive Diseases Week 2026 in early May, are promising.
The researchers found that patients who received the sham procedure regained about 40% more weight than those who underwent DMR.
The treatment group regained just seven pounds on average — maintaining more than 80% of their weight loss — while the control group regained roughly double that amount.
Participants who underwent DMR also reported reduced cravings for sweets in questionnaires.
“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,” Sullivan said. “That gives us confidence that we’re targeting the right biology.”
Even more promising: No serious complications were reported.
“Other than recovering from the general anesthesia, there isn’t much recovery time involved,” Sullivan said. “You can be back to your daily routine in about a day.”
In the study, participants in the DMR group underwent the procedure one week after stopping tirzepatide.
Looking ahead, the researchers hope to refine the treatment protocol and test whether it could help maintain weight loss in other situations, such as after dieting.
“If approved, DMR could work for most people who achieved meaningful weight loss with a GLP-1,” Sullivan said. “We may find in the future that DMR can also prevent weight gain for patients who lose weight with other methods.”
The timing matters more than ever.
Across the US, about 40% of adults are considered to be obese, and projections suggest that number could surpass 65% by 2050 without intervention.
The stakes are high.
Obesity is a chronic disease linked to serious complications, including Type 2 diabetes, heart disease, hypertension and stroke.
It also raises the risk of a range of other conditions, including fatty liver disease, sleep apnea, osteoarthritis and several types of cancer.
Taken together, these ripple effects drive higher health care costs, a reduced quality of life and shorter life expectancy. Studies estimate that about 1 in 6 deaths in the US each year are linked to excess weight or obesity.
