Protocol Outlines Comparison of Endoscopic Gastric Botulinum Toxin Injections and Liraglutide for Obesity Treatment

Obesity represents a significant global public health crisis, contributing to a myriad of comorbidities including type 2 diabetes, cardiovascular disease, and certain cancers. While bariatric surgery offers the most substantial and durable weight loss, it is an invasive procedure with inherent risks, high costs, and is not suitable for all patients. Pharmacological interventions, particularly Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) like Liraglutide, have emerged as effective non-surgical options, promoting weight loss by enhancing satiety and slowing gastric emptying via activation of the GLP-1R. However, these require chronic administration and can have side effects. There is a critical unmet need for less invasive, yet highly effective, alternatives or complementary strategies for weight management, especially for patients seeking significant results without daily medication or major surgery. Endoscopic interventions, such as targeted gastric botulinum toxin injections, offer a promising, minimally invasive approach by directly modulating gastric motility, potentially providing a novel therapeutic avenue. This study aims to directly compare such an endoscopic method against a established GLP-1RA.

This prospective, comparative study protocol outlines the evaluation of two distinct interventions for obesity over a 16-week follow-up period. Both interventions will be combined with a standardized lifestyle modification program, including a 2000 kcal diet for men or 1800 kcal diet for women, alongside moderate daily aerobic exercise (at least 30 minutes, 5 times a week). The Botulinum Toxin A (BTA) group will undergo esophagogastroduodenoscopy (EGD) with endoscopic ultrasound (EUS) guidance. Five injections of Botulinum Toxin A (BTA) at 20 U each will be precisely administered into the gastric antral muscularis propria, 2 to 3 cm proximal to the pylorus, totaling 100 U. Patients will be monitored for complications. The GLP-1 group will receive Liraglutide subcutaneous once daily, initiating at 0.6 mg and gradually escalating up to a maximum of 3 mg daily, based on patient tolerability. The primary endpoint for both groups will be weekly body weight assessment.