Gut procedure may help patients keep weight off after stopping tirzepatide

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 duodenal mucosal resurfacing helped a small group of patients maintain up to 80% of their weight loss after they stopped taking tirzepatide. Findings presented at medical meetings are considered preliminary until published in a peer-reviewed journal.

Regaining the weight you’ve just lost is a major risk for anyone who decides to stop Ozempic or Zepbound. Researchers said weight regain occurs in the vast majority of patients who stop these medications, and the metabolic benefits are lost.

The procedure 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. This “gut reset” has previously been investigated as a treatment for type 2 diabetes.

For the current study, researchers tested whether this metabolic reset could help people keep weight off after stopping their GLP-1 drug. 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. High-fat and high-sugar diets can cause changes in the inner lining of the duodenum, rewiring how the gut responds to food. 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.

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. Those who’d had more gut resurfaced had regained just 7 pounds, maintaining over 80% of their weight loss. Those in the control group regained about double that amount. The difference in weight regain between the two groups also appeared to widen from one to six months following the procedure.

Researchers said they 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.