Abstract Disclosure: J.M. Deirmenjian: None. C. Dagher: None. Gastroparesis is characterized by a delay in gastric emptying that may present with nausea, vomiting, satiety, abdominal pain, and anorexia. The most common cause of gastroparesis is diabetes mellitus due to vagal autonomic neuropathy which prevents coordinated gastric contractions. Medications may also induce gastroparesis. Glucagon-like peptide (GLP)- 1 agonists such as semaglutide are being prescribed for diabetes control but also due to benefits of cardiovascular disease and weight loss. Concerns of GLP-1 agonists causing gastroparesis are valid as the mechanism of action includes delaying gastric emptying, especially with newly developed analogs that are more potent with longer half-lives. Patient is a 43-year-old female with a history of hypertension, uncontrolled diabetes mellitus type 2, diabetic gastroparesis, diabetic neuropathy, hyperlipidemia, and obesity who presented with a one-month history of postprandial abdominal pain, nausea, vomiting, and a 40-pound unintentional weight loss with decreased oral intake. Her abdominal pain was sharp and was exacerbated with eating. While she had several gastroparesis flares in the past, she was in remission for almost two years until she was transitioned from dulaglutide to semaglutide after which she had a recurrent flare after two doses. On physical examination, her abdomen was diffusely tender to palpation.On admission, her hemoglobin A1c was 9.7%. She was made NPO, started on peripheral fluids, and initiated on scheduled metoclopramide given high suspicion of a gastroparesis flare. She underwent a gastric emptying study with the gastric amount retained as follows: 97% (at 1 hour), 88% (at 2 hours), and 79% (at 4 hours). Her hospital course was complicated by persistent symptoms of gastroparesis. Gastroenterology recommended scheduled metoclopramide and erythromycin for motility and dietary adjustments including small volume liquid calories. Her oral intake was insufficient and she opted for total peripheral nutrition until symptoms improved. She was advised to never take a GLP-1 agonist again and should her symptoms not improve the next step would be to pursue a gastric pacemaker. The etiology of the patient’s gastroparesis was uncontrolled diabetes. The proximity between starting semaglutide and symptom onset is compelling as an inciting factor in this flare. This admission’s gastric emptying study results showed higher gastric retention for a longer period of time, which may shed light to the potency of these new GLP-1 analogs. The patient tolerated maximum dose dulaglutide for months but not even two doses of semaglutide. With the race to invent more potent GLP-1 agonists for diabetes control and weight loss on the horizon, knowing their side effects and mechanism of action is crucial. While not listed as a contraindication, there should be hesitancy to offer these agents to anyone with significant gastroparesis. Presentation: 6/2/2024