Across 12 case reports encompassing 13 patients, GLP-1 receptor agonists — predominantly semaglutide, followed by liraglutide, dulaglutide, and exenatide — were associated with clinically confirmed gastroparesis. Symptom onset ranged from hours to months post-initiation, frequently triggered by dose escalation or inappropriate re-initiation. Presentations included nausea, vomiting, bloating, early satiety, and oral intolerance, with imaging or endoscopy revealing gastric distension or retained contents without mechanical obstruction. Critically, discontinuing the offending agent resolved symptoms in every reported patient.
With tens of millions now prescribed semaglutide and related GLP-1 agonists globally for diabetes and weight loss, this safety signal carries outsized public health weight despite the small evidentiary base. GLP-1 receptors are expressed throughout the enteric nervous system, and the drugs' known gastric-motility-slowing mechanism makes gastroparesis a biologically plausible — not merely incidental — complication. The finding that non-diabetic patients were also affected is particularly notable: diabetic gastroparesis has an established aetiology, but idiopathic GLP-1-induced gastroparesis in otherwise healthy individuals reframes the risk profile for the obesity-treatment population. The evidence here is severely limited — 13 patients, no controls, no incidence rate — making it hypothesis-generating rather than definitive. It cannot quantify absolute risk. Clinicians should nonetheless adopt lower diagnostic suspicion thresholds for gastroparesis in any GLP-1RA user presenting with upper GI symptoms, especially after dose uptitration, and consider drug withdrawal before invasive workup.