S4128 Side Effects of GLP-1 Agonists: A Case of Colonic Pseudo-Obstruction

Introduction: Glucagon-like peptide-1 (GLP-1)–based therapies used in diabetes treatment have shown benefits with respect to weight loss and are a go-to medication, particularly in patients with existing atherosclerotic cardiovascular disease, high Hemoglobin A1c and hypoglycemia risk. The most frequently reported side effects of GLP-1 agonists are nausea, vomiting, and diarrhea. Several studies have found an increased risk of other GI adverse events such as biliary disease, pancreatitis, bowel obstruction, and gastroparesis. Case Description: Thirty-five-year-old woman with lower abdominal pain that was initially dull, aching radiating to her back, continuous, progressively worsened, severe at the time of presentation. Associated with multiple episodes of nausea and vomiting. Patient mentioned taking GLP-1 for the last 3 months with recent dose increase. Computed tomography (CT) abdomen/pelvis with intravenous contrast showed a dilated colon with increased stool in the rectum, numerous fluid-filled loops of the bowel, and wall thickening involving the descending colon. Esophagogastroduodenoscopy showed a moderate amount of food retained in gastric body with gastroparesis possible; esophageal biopsy showed no pathology. A gastric emptying study showed standard transit time. Overnight, the patient was transferred to the intensive care unit due to hypotension and was started on pressors, fluids, and broad-spectrum antibiotics. Repeat CT of the abdomen/pelvis showed marked dilation of the entirety of the large bowel with multiple air-fluid levels. Patient underwent an emergent midline laparotomy with an ostomy. Considering her history of recent increase in GLP-1, it was suspected the symptoms were likely due to GLP-1 induced colonic pseudo-obstruction. Discussion: GLP-1, an incretin hormone produced by the L cells of the small intestine, binds to the GLP-1 receptor expressed by various organs. It stimulates insulin release from the pancreas and reduces gastric emptying and food intake by promoting satiety and inhibiting post-meal glucagon release. It also directly affects the hypothalamus, leading to early satiety. GLP-1 is approved for weight loss in patients with a body mass index (BMI) of 30 or higher, or those with a BMI of 27 or higher with diabetes or hypertension. The most common adverse effects of GLP-1 include gastrointestinal symptoms such as decreased appetite, abdominal pain, dyspepsia, bowel obstruction, and gastroparesis. These symptoms can occur in up to 70% of patients and may worsen with higher doses. They are more severe within the first 4 weeks of therapy or with sudden escalation of treatment.