Endoscopic mucosal ablation—designed to alter the gastric lining and minimize the production of ghrelin—may help patients achieve weight loss.

Feelings of hunger originate in the gastric fundus when the chamber empties, leading to increased production of ghrelin, the primary hormone that triggers hunger and controls appetite. As the gastric fundus fills with food, hunger subsides, and ghrelin production diminishes. Ghrelin levels are typically higher in patients with obesity and also rise when individuals lose weight, making it challenging to maintain weight loss.

Historically, the most effective method for reducing ghrelin production was to surgically remove or bypass the gastric fundus. There are currently no pharmacologic treatments to reduce ghrelin. Anti-obesity drugs like semaglutide employ a different hormonal pathway: glucagon-like peptide (GLP)-1.

“Obesity is [a] chronic, lifelong disease that is predicted to affect nearly half of the U.S. population by 2030. Its effect on overall health, quality of life, and global health-care costs is massive, and we need as many treatment options as possible,” stressed Christopher McGowan, MD, Medical Director and a gastroenterologist at the True You Weight Loss clinic in North Carolina.

In the study, presented at Digestive Disease Week 2024 (Abstract 516), 10 female patients with obesity underwent endoscopic mucosal ablation and completed validated questionnaires. The procedure involves the insertion of fluid to protect underlying gastric tissue, followed by ablation of the mucosal lining of the gastric fundus to reduce the number of ghrelin-producing cells.

The researchers found that following endoscopic mucosal ablation, patients experienced a 42%, over 40%, and 7.7% reduction in stomach capacity, fasting ghrelin levels, and body weight, respectively. Further, the patients self-reported that their hunger was diminished by more than one-third.

The investigators emphasized that if endoscopic mucosal ablation is proven effective over longer periods of time and in larger trials, it could complement endoscopic sleeve gastrectomy or be offered as a one-time procedure that replaces or complements other treatments.

“Obesity and weight are very complex and regulated by multiple hormone pathways. This relatively brief, outpatient, nonsurgical procedure alters one of these many pathways that make it difficult for [patients] to lose weight and maintain weight loss, can facilitate weight loss, significantly curb hunger, and … could be an additional option for patients who don’t want or aren’t eligible for anti-obesity medications, such as [semaglutide], or bariatric surgery,” Dr. McGowan highlighted. “This is just the beginning. The first question was whether we [could] endoscopically reduce hunger and ghrelin. The answer is: yes, we can.”