They raise and lower the risk for different reasons, at different times
STUDY: Xie Y et al, BMJ Medicine 2026
STUDY TYPE: Cohort study (target trial emulation)
FUNDING: US Department of Veterans Affairs
Background
Pancreatitis is a rare side effect of GLP-1 receptor agonists. But these medications may indirectly lower the risk of pancreatitis by improving metabolic health (weight, glucose, triglycerides) and reducing alcohol use and triglyceride levels. This study looks at how those risks balance out.
The Study
- 333,687 veterans with type 2 diabetes starting either a GLP-1 receptor agonist (n=132,551) or a sulfonylurea (n=201,136) between 2017 and 2023.
- Followed for 12 months; pancreatitis cases classified by cause: drug-induced, alcohol-related, triglyceride-related, biliary, or idiopathic.
- Semaglutide accounted for 66% of GLP-1 prescriptions.
Results
Overall pancreatitis rates were nearly identical between groups at one year. But lumping all causes together masked opposing effects.
GLP-1s raised the risk of suspected drug-induced pancreatitis — and this risk was front-loaded, with 42% of excess cases occurring in the first three months. Meanwhile, GLP-1s cut alcohol-related pancreatitis (reduction concentrated in months 4–6) and triglyceride-related pancreatitis (months 10–12). The two effects offset each other almost exactly. Biliary and idiopathic pancreatitis were unchanged.
Limitations
The cohort was mostly older men, limiting generalizability. Drug-induced pancreatitis is a diagnosis of exclusion; those cases are labeled “suspected.” Milder cases managed in outpatient settings weren’t captured. Residual confounding can’t be ruled out.
Practice Implications
- The pancreatic risks are real, but balance out, especially for people with excessive alcohol use.
- We see a similar pattern with valproate, which has liver risks but improves liver health when used to reduce drinking in alcohol use disorder.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
