Pancreatitis
Inflammation of the pancreas causing severe abdominal pain, elevated pancreatic enzymes, and potential complications. Pancreatitis has been identified as a safety signal for GLP-1 receptor agonists, though large trials show mixed results. All GLP-1 RA prescribing information includes pancreatitis warnings.
Technical Context
Acute pancreatitis: diagnosed by 2 of 3 criteria — characteristic abdominal pain (severe epigastric, radiating to back), serum amylase or lipase >3× upper limit of normal, and imaging findings (CT/MRI). Severity ranges from mild (interstitial oedematous, self-limiting) to severe (necrotising, organ failure, mortality 20-40%). GLP-1 RA-pancreatitis relationship: early post-marketing reports raised concern. Large CVOTs provided mixed evidence — most showed no statistically significant increase in adjudicated pancreatitis, though numerical imbalances were observed in some trials. Meta-analyses suggest a small potential increase in risk (OR ~1.1-1.5). Mechanistic plausibility: GLP-1R activation stimulates pancreatic exocrine secretion and may promote ductal cell proliferation. Current position: pancreatitis is listed as a warning/precaution (not contraindication) for all GLP-1 RAs. Patients should report persistent severe abdominal pain. GLP-1 RA should be discontinued if pancreatitis is confirmed.