Gastroparesis
Delayed gastric emptying causing nausea, vomiting, and abdominal discomfort. GLP-1 receptor agonists deliberately slow gastric emptying as a therapeutic mechanism, raising concern about whether this can progress to clinically significant gastroparesis in some patients. Regulatory investigation is ongoing.
Technical Context
Gastroparesis is diagnosed by delayed gastric emptying (>10% retention at 4 hours on scintigraphic gastric emptying study) in the absence of mechanical obstruction. GLP-1 RAs deliberately slow gastric emptying through vagal and direct smooth muscle mechanisms — this is a therapeutic effect (reducing postprandial glucose spikes and prolonging satiety). The clinical question is whether pharmacological delayed gastric emptying can progress to pathological gastroparesis in susceptible individuals. FDA investigation: FAERS analysis identified gastroparesis signals; the FDA requested additional data from manufacturers. Tachyphylaxis to the gastric emptying effect may occur with chronic GLP-1 RA use (the initial slowing attenuates over weeks). Risk factors for GLP-1 RA-associated gastroparesis may include: pre-existing gastric motility disorders, diabetes-related autonomic neuropathy, and concurrent use of other motility-reducing drugs.