S4133 Semaglutide-Associated Portal Vein Thrombosis: A Rare Vascular Complication

Introduction: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved for obesity and type 2 diabetes, is commonly associated with gastrointestinal adverse effects; however, its vascular complications are not well characterized. While thrombotic events remain rare, isolated cases of splanchnic venous thrombosis have been reported. We present a case of portal vein thrombosis in a patient on semaglutide with significant recent weight loss and an improving metabolic profile, raising concern for a potential drug-related effect. Case Description: A 56-year-old obese man with no thrombotic history presented with 2 weeks of nausea, bilious vomiting, diffuse abdominal pain, and non-bloody diarrhea. Symptoms began shortly after his semaglutide dose was increased to 2.4 mg weekly. He had recently lost 25 lb over 6 months and was engaging in regular physical activity. He was hemodynamically stable with normal lactate. Computed tomography imaging revealed pneumatosis intestinalis, concerning for early intestinal ischemia, and a portal vein filling defect. Doppler ultrasound confirmed diminished hepatopedal flow consistent with partial portal vein thrombosis. He was managed conservatively with bowel rest, intravenous fluids, and therapeutic anticoagulation, while semaglutide was held, given the temporal relationship. Discussion: This case raises concern for a possible association between semaglutide and venous thrombosis, particularly in the setting of gastrointestinal intolerance and dehydration. Although obesity is a known prothrombotic state, our patient had demonstrated reduced risk with sustained weight loss and increased physical activity. No other provoking factors or hypercoagulable states were identified. The close temporal association with semaglutide dose escalation supports a potential drug effect. Prior reports of splanchnic thrombosis with GLP-1 RA suggest this may be an underrecognized complication. Physicians should consider vascular events in patients with persistent gastrointestinal symptoms while on semaglutide, especially following dose escalation.