Endoscopic ablation reduces primary hunger hormone by up to 53% in obesity
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Key takeaways:
- Endoscopic ablation of the gastric fundus reduced circulating ghrelin and ghrelin cells by 45% and 53% at 6 months.
- Stomach capacity decreased by 42% and total body weight loss by “approximately 19 pounds.”
Endoscopic ablation of the gastric fundus reduced ghrelin, the primary hunger hormone, and resulted in significant weight loss among a small cohort of female patients with obesity, according to research.
“Ghrelin is a key hormonal regulator of weight and obesity,” Christoper McGowan, MD, CEO and founder of True You Weight Loss in North Carolina, said at the Digestive Disease Week media briefing. “Interestingly, 80% to 90% of it is produced in one location, which is in the inner lining of the gastric fundus— the very top of the stomach. Currently, the only proven way to reduce ghrelin is to surgically remove or bypass the fundus and the current weight loss medications ... do not impact ghrelin directly.”
He continued: “There is no existing targeted treatment for this key hunger and weight hormone.”
In a first-in-human trial, McGowan and colleagues investigated whether endoscopic fundic mucosal ablation with a dual-channel endoscope and Hybrid argon plasma coagulation would reduce ghrelin, hunger and weight among 10 female patients (mean age, 38.4 years; mean BMI, 40.2) with obesity. The primary outcome measure was change from baseline in fasting plasma ghrelin at 6 months.
Researchers measured fasting plasma ghrelin; maximum tolerated volume of standard drink test, which is an indication of satiation and accommodation; and weight at baseline and months 1, 2, 3 and 6. Participants also completed Daily Eats and Weight Efficacy Lifestyle Questionnaire Short-Form questionnaires at each time point and underwent repeat endoscopic assessment at month 6.
Results demonstrated a contracted fundus among all participants at month 6. Circulating ghrelin and ghrelin cells decreased by 45% and 53%, respectively; stomach capacity decreased by 42%; and hunger, appetite and cravings decreased by 43%. Total body weight loss was “approximately 19 pounds or an average of just under 8% of body weight at 6 months,” McGowan said.
Further, there was a decrease in mean hunger score from 6.2 to 4, as measured by the Daily Eats questionnaire, as well as a decrease in mean Eating Drivers Index from 7 to 4. Composite Weight Efficacy Lifestyle Questionnaire Short-Form questionnaire score improved from 47.7 to 62.4.
Researchers reported no serious adverse events.
“Endoscopic ablation of the gastric fundus does lead to clinically and statistically significant decreases in ghrelin, hunger, capacity and weight,” McGowan said. “The technique was shown to be safe, it’s outpatient and completely nonsurgical. This may represent, and frankly, should represent a treatment option for the greater than 100 million U.S. adults with obesity.”
Perspective
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Matthew Kroh, MD, FACS, FASMBS, FASGE
This study highlights the significant impact of endoscopic ablation of the gastric fundus on reducing ghrelin levels and promoting weight loss in patients with obesity, a worldwide epidemic.
By targeting the primary production site of ghrelin — a key hormone that regulates hunger — this technique decreased ghrelin and ghrelin cells by 45% and 53%, respectively, alongside a notable reduction in stomach capacity and an average weight loss of approximately 19 pounds over 6 months. These are promising but early results, as the study was conducted with a small cohort of only 10 patients at a single institution and with a short follow-up period. These constraints may skew the perceived effectiveness and safety of the treatment.
Still, the findings are important, as they offer a relatively simple and likely reproducible, nonsurgical method to address hormonal factors in obesity, potentially expanding treatment approaches and broadening the scope of interventions to treat obesity. However, the limited demographic and short observational timeframe necessitate cautious interpretation of the outcomes, underscoring the need for larger-scale, longer-term studies to validate these preliminary findings comprehensively.
This novel endoscopic therapy, in conjunction with existing endoscopic approaches and expanding anti-obesity medications, will open more obesity treatment options for patients. Larger and longer studies of this particular technology will further guide us in how best to potentially implement this for better outcomes for our patients.
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McGowan C, et al. Endoscopic ablation of the gastric fundus in adults with obesity: A first in human study. Presented at: Digestive Disease Week; May 18-21, 2024; Washington (hybrid).
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