Written by Peter Liu
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GLP1 agonist use was associated with better pancreatitis outcomes in a retrospective study of patients with type 2 diabetes.
Plot twist – could GLP1 agonists actually protect from pancreatitis?
Pancreatitis has always been listed as a contraindication to GLP1 agonist therapy, due to early signals that its use was linked to higher risk of pancreatitis. However, the jury is still out on whether there is a true causal link. There is no RCT-level evidence for this association to date.
A recent propensity-matched retrospective cohort study suggests a possible opposite effect of GLP1 agonists. Using international data from the TriNetX registry, 29,423 patients treated with GLP1 agonists for type 2 diabetes that had no pancreatitis-related comorbidities were matched to 20,459 patients with type 2 diabetes who were not on GLP1 agonists but were equally likely to have been put on GLP1 agonist therapies based on available demographics. There was a decreased likelihood of developing pancreatitis with GLP1 agonist use, though this was not statistically significant (HR 0.75; 95% CI 0.49-1.01). For patients taking GLP1 agonists who developed pancreatitis, there was a significantly lower risk of complicated pancreatitis (HR 0.32), parenteral nutrition needs (HR 0.28), sepsis (HR 0.71), AKI (HR 0.54), shock (HR 0.52), and mechanical ventilation support during admission (HR 0.23), all statistically significant.
This supports growing sentiment that GLP1 agonists may not increase risk of pancreatitis, and implies a possible protective effect. However, the limitations of this retrospective study design makes its findings uncertain without support from future confirmatory studies.
How does this change my practice?
It is unlikely that I will ignore active drug labeling that list pancreatitis as a contraindication to GLP1 agonist use. However, unlike concerns with medullary thyroid cancer and MEN 2A and 2B, pancreatitis is not an absolute contraindication to GLP1 agonist use. In a subset of patients with a history of pancreatitis who have been counseled on the current uncertainty in GLP1 effects on this condition, one could make the case for its use.
Source
Glucagon-Like Peptide-1 Receptor Agonists Use Does Not Increase the Risk for Acute Pancreatitis and Is Associated With Lower Complications in Patients With Type 2 Diabetes Who Develop Acute Pancreatitis: A Multicenter Analysis. Am J Gastroenterol. 2025 May 13. doi: 10.14309/ajg.0000000000003525. Epub ahead of print. PMID: 40358430
