<p>In study, we compared safety, feasibility, and efficacy of endoscopic ultrasound (EUS) guided botulinum toxin A (BTA) injection versus glucagon like peptide 1 (GLP-1) agonists in treatment of obesity. The two intervention techniques were paired with a number of lifestyle changes, such as a diet of 2000 cal per day for males and 1800 cal per day for women, and moderate daily cardiovascular exercise (at least 30 min, 5 days a week) for 4 months. Over the course of a 16-week follow-up period, body weight was measured. Forty patients were included in this study, 20 in each group. The 1st group underwent BTA injections via EUS, while the 2nd group received GLP 1 receptor agonist. In the 1st group, there was a significant weight loss from (107.30 ± 11.41 kg) at baseline to (94.75 ± 12.65 kg) after 4 months of treatment (<i>p</i> value &lt; 0.001). In the 2nd, there was significant weight loss from (123.28 ± 17.17 kg) at baseline to (109.75 ± 14.37 kg) after 4 months (<i>p</i> value &lt; 0.001). Significant reduction of BMI was reported in both groups after 4 months of treatment; 1st group, from (40.53 ± 4.41 kg/m²) at baseline to (35.78 ± 4.82 kg/m²) (<i>p</i> value &lt; 0.001), 2nd group from (44.15 ± 5.94 kg/m²) to (39.40 ± 5.68 kg/m²) (<i>p</i> value &lt; 0.001). Both measures are effective, but we have to consider the invasiveness of the first one and the systemic side effects of the second procedure.</p><p><b>Trial registration</b>: NCT05268627, First registration date (27/03/2022).</p>