• Posted April 27, 2026

Regaining Weight After Quitting Your GLP-1 Drug? A Simple Procedure Might Help, Study Says

Regaining the weight you’ve just lost is a major risk for anyone who decides to stop taking Ozempic or Zepbound.

But an experimental outpatient gut procedure might help people transition off their GLP-1 weight loss drug without packing on the pounds, according to new research scheduled for presentation at the Digestive Disease Week meeting in Chicago.

This simple “gut reset” helped a small group of patients maintain up to 80% of their weight loss after they stopped taking tirzepatide (Mounjaro/Zepbound), researchers found.

“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 lead researcher Dr. Shelby Sullivan, director of the Endoscopic Bariatric and Metabolic Program at Dartmouth Health Weight Center in Lebanon, New Hampshire.

“But if they stop these medications, weight regain occurs in the vast majority of patients, and the metabolic benefits are lost,” she said in a news release. “Finding a treatment that allows patients to stop these medications without weight regain or loss of metabolic benefit is a huge unmet need.”

The procedure, called duodenal mucosal resurfacing, involves a small thin tube that’s run through the GI tract to the duodenum – the upper part of the small intestine that sits just below the stomach.

Through the tube, doctors apply heat to burn off the unhealthy inner lining of duodenum, stimulating the growth of new healthy tissue, researchers said.

This “gut reset” has previously been investigated as a treatment for type 2 diabetes, according to the Mayo Clinic.

For the current study, researchers tested whether this metabolic reset could help people keep weight off after stopping their GLP-1 drug.

Glucagon-like peptide-1 (GLP-1) drugs mimic the GLP-1 hormone, which helps control insulin and blood sugar levels, decreases appetite and slows digestion of food. 

The resurfacing takes place at the location in the gut where the hormones mimicked by GLP-1 drugs are produced, Sullivan said.

High-fat and high-sugar diets can cause changes in the inner lining of the duodenum, rewiring how the gut responds to food, Sullivan said. 

The resurfacing procedure is intended to reset a person’s metabolism to their new weight to help them keep off the pounds they’ve lost.

The team recruited 45 people who had lost at least 15% of their total body weight on tirzepatide — around 40 pounds on average — but were quitting the drug.

Researchers randomly selected 29 to undergo the outpatient procedure, and the rest to receive a sham procedure.

“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. Participants could not tell if they had the sham or real procedure because there are not a lot of symptoms after the procedure.”

Six months after quitting tirzepatide, those who got the sham procedure had regained 40% more weight than those who got the real gut reset, the study found.

Meanwhile, those who’d had more gut resurfaced had regained just 7 pounds, maintaining over 80% of their weight loss, researchers said. Those in the control group regained about double that amount.

The difference in weight regain between two groups also appeared to widen from one to six months following the procedure, researchers noted.

“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.” 

The researchers will continue to follow these patients and track their weight over time.

A larger clinical trial of the procedure involving more than 300 people is now underway, with early data expected later this year, researchers said.

Sullivan is to present these results May 4 at the Digestive Disease Week meeting, which is jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract.

Findings presented at medical meetings are considered preliminary until published in a peer-reviewed journal.

More information

The Mayo Clinic has more on duodenal mucosal resurfacing.

SOURCE: Digestive Disease Week, news release, April 23, 2026