- A novel, minimally-invasive procedure that targets the “hunger hormone” ghrelin could someday help treat obesity.
- The procedure uses endoscopic ablation to burn targeted areas of the stomach lining to reduce the production of ghrelin.
- Participants in the small, six-month trial showed weight loss, lower fasting ghrelin, and reported being less hungry.
A new minimally-invasive procedure that targets the production of the “hunger hormone” ghrelin in the stomach is showing promise in early-stage trials.
Researchers conducted a six-month trial involving endoscopic ablation of the gastric fundal mucosa — literally the burning of the stomach lining — to reduce ghrelin production and help patients lose weight.
They will present their findings at Digestive Disease Week (DDW) 2024. This research has yet to be published in a peer-reviewed scientific journal.
“This relatively brief, outpatient, non-surgical procedure can facilitate weight loss and significantly curb hunger, and it could be an additional option for patients who don’t want or aren’t eligible for anti-obesity medications, such as Wegovy and Ozempic, or bariatric surgery,” said lead author Christopher McGowan, MD, a gastroenterologist and medical director of True You Weight Loss, a physician-owned clinic based in North Carolina, in a press release.
Experts contacted by Healthline said that the procedure demonstrates a solid proof of concept, but will need more rigorous trials before it is clear whether the procedure is ultimately safe and effective for weight loss.
“There’s a signal there, but clearly it’s very early data,” Dan Azagury, MD, section chief of Minimally Invasive and Bariatric Surgery and medical director for the Bariatric and Metabolic Interdisciplinary clinic at Stanford Health, told Healthline.
Jihad Kudsi MD, ABOM, a bariatric surgeon, CEO and founder of TeleSlim Clinic, Medical Director of Bariatric Surgery at the University of Chicago, and spokesperson for the Obesity Society, told Healthline, “The initial weight loss results appear promising…However, it’s essential to emphasize that long-term weight maintenance is the paramount consideration in any weight loss intervention discussion. Evaluating the procedure’s long-term results is crucial to fully understanding its effectiveness and sustainability.”
Procedure cut “hunger hormone” levels by 48%
The six-month first-in-human trial involved 10 female patients with obesity, a BMI of 30 or above, and an average age of 38 years old. Each participant received an endoscopic fundic mucosal ablation procedure.
Endoscopic mucosal ablation is an established minimally-invasive procedure that is used to remove small nodules, growths, and even early cancers in and around the esophagus. The procedure has not previously been established for weight loss.
“This ablation technology is pretty widely used in endoscopy. The difference with this trial is that they go and they aim for this area of the fundus. The idea is that the cells there then no longer have the capacity to secrete ghrelin,” said Azagury.
Doctors target the fundic mucosa for ablation because it is where ghrelin and other hormones are secreted. Ghrelin, aptly called the “hunger hormone,” plays a role in making you hungry when you haven’t eaten and feeling satiated after a meal.
Over the six-month observation period, researchers observed that participants not only lost weight, about 7% on average, but also showed a nearly 50% drop in fasting ghrelin levels. Other positive weight-loss indicators from the trial were also documented, namely that participants self-reported being less hungry, and their stomachs shrank — some by as much as 42%.
There were also no apparent safety issues, as no serious adverse events were reported.
A new way to treat obesity?
The procedure represents a novel, minimally-invasive procedure with the potential to help tackle the obesity epidemic. Bariatric surgery, in which the stomach is manipulated to make it smaller, is considered the gold standard for weight-loss, but it is still surgery. Endoscopic procedures, on the other hand, can utilize the esophagus or small incisions to be performed.
While some bariatric procedures such as endoscopic sleeve gastroplasty and intragastric balloon placement typically affect ghrelin production indirectly, they do not directly target it like endoscopic ablation.
“ESG not only reduces the size of the stomach but also decreases ghrelin and enhances GLP-1 secretion…Intragastric balloons have been associated with changes in hormone levels, including ghrelin, which may contribute to their weight loss effects,” said Kudsi.
Breakthrough GLP-1 drugs like Ozempic, Wegovy, and Zepbound, have proven to be incredibly effective at treating obesity, but do so through a separate hormonal pathway. They don’t target ghrelin, but work on the “GLP1” or the glucagon-like peptide 1 hormone of the gut, which also plays a role in hunger and satiety.
With obesity, picking the right therapy is rarely an either/or situation; instead, doctors must rely on a variety of treatment options to ensure patients are successful over the long term.
“Obesity is a very complex disease. It’s a very difficult disease to treat. It’s a lifelong disease. So this is something that you need multiple modalities in order to be able to treat successfully,” said Azagury.
“Having this armamentarium of different options is really necessary.”
The bottom line
A minimally-invasive endoscopic procedure that targets the “hunger hormone” ghrelin appears promising after an initial six-month trial.
Participants in the first-in-human trial showed weight loss, lower fasting ghrelin levels, and reported less hunger compared to baseline.
Experts say that there’s still much more work to be done before it’s clear if the procedure is safe and effective over the long term.
