SUN-645 - Superior Mesenteric Artery Syndrome Following GLP-1 Receptor Agonist-Associated Weight Loss

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide metabolic and cardiovascular benefits that correlate with the degree of weight loss achieved. A 5% reduction offers improved glycemic control and cardiovascular risk factors while a 10% weight reduction offers remission of type 2 diabetes and reduced cardiovascular mortality. However, their use is often limited by dose-dependent gastrointestinal side effects including nausea, vomiting, diarrhea, and constipation which may occur in up to 50% of patients early in therapy. More serious complications, including pancreatitis, gallbladder disease, gastroparesis, and bowel obstruction, have also been reported. Superior mesenteric artery (SMA) syndrome is a rare cause of proximal intestinal obstruction due to compression of the third portion of the duodenum between the superior mesenteric artery and aorta, typically from loss of the mesenteric fat pad. It is most commonly seen in hypermetabolic or cachectic states, including patients with bariatric surgery or eating disorders. We present a case of SMA syndrome following GLP-1 RA-associated weight loss and development of a pancreatic pseudocyst.

Case: A 76-year-old woman with hypertension, AV block requiring pacemaker, and type 2 diabetes mellitus on metformin, with prior cholecystectomy, presented with several days of worsening epigastric pain, nausea, reflux, and decreased appetite. She had started tirzepatide six months prior, with recent dose escalation to 7.5 mg weekly. Her weight decreased from 160 lbs to 115 lbs over two years (28% reduction), including a decline from 130 lbs to 115 lbs (12% reduction) during tirzepatide therapy. CT imaging revealed a 9.5 cm pancreatic pseudocyst causing gastric and proximal small bowel dilation. She underwent EGD with AXIOS cystogastrostomy stent placement with initial improvement. One month later, tirzepatide was discontinued and the stent was exchanged. She returned the following day with severe epigastric pain and bilious vomiting. Repeat CT showed improvement in the pseudocyst but worsening obstruction with a transition point at the third portion of the duodenum and marked gastric dilation, consistent with SMA syndrome. She required balloon dilation and PEG-J placement for enteral nutrition.

Discussion: SMA syndrome is a rare (~0.1–0.3%) but important complication associated with weight loss. Data suggests that reductions as low as 5% of body weight may precipitate symptoms, particularly in patients with low BMIs at baseline or anatomic predispositions. With increasing use of GLP-1 RAs, clinicians must be aware of both rare complications associated with weight loss and common gastrointestinal side effects. With no previously published cases of SMA syndrome with GLP-1 RAs, this case marks an important teaching point and need for increased vigilance.

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