GLP-1 Use in Patients with Prior Alcohol-Related Pancreatitis Dangerously Increases DKA, Mortality Risk

Patients with a prior history of alcohol-related pancreatitis saw substantially increased risks of recurrent pancreatitis, mortality, sepsis, and diabetic ketoacidosis (DKA) up to 5 years after initiating GLP-1 RA or dual GIP/GLP-1 agonists.1

GLP-1 RAs are among the most prominent treatments for type 2 diabetes mellitus (T2DM) in recent years, due to their impressive capacity for improving blood sugar control and cardiovascular health in addition to significant and persistent weight loss. However, evidence is severely limited regarding the association between GLP-1s and pancreatitis.2

Previous research has indicated that the use of GLP-1s in a comorbidity-free population of patients with T2DM did not increase their risk of pancreatitis. However, given that many patients with alcohol-related pancreatitis are largely excluded from similar research and are therefore understudied, further research is necessary. This is especially true given the immense prominence of GLP-1 RAs in modern diabetes treatment.2

The present data were presented at the American Association of Clinical Endocrinology Annual Meeting 2026 in Las Vegas, Nevada, by Esra’a Alshdifat, MD, an endocrinology fellow at Lincoln Hospital. Alshdifat and colleagues attempted to bridge the existing gap between GLP-1 RAs and patients with prior alcohol-related pancreatitis.1

The team conducted a multicenter retrospective cohort study, examining patients ≥18 years of age with T2DM or obesity who had initiated GLP-1 RA or dual GIP/GLP-1 RA. Data were collected from the TriNetX database, and the included patients were analyzed using 1:1 propensity score matching, with adjustment for major pancreatitis confounders. Patients were followed up for a total of 5 years.1

A total of 4558 patients were ultimately enrolled in the trial, with 2279 assigned to both the prior pancreatitis and control cohorts. Following propensity score matching, Alshdifat and colleagues noted well-balanced baseline characteristics with no significant differences in clinical risk factors or demographics.1

After 5 years, patients with prior alcohol-related pancreatitis displayed substantially increased risks of DKA, sepsis, mortality, and acute pancreatitis following initiation of incretin therapy. Alshdifat and colleagues note that these results support an increased degree of caution and the careful selection of patients when prescribing incretin therapies, given this population’s apparent high risk. Additionally, the team calls for further prospective studies to define the treatment’s safety.1

“Prior pancreatitis history should influence incretin therapy decisions,” Alshdifat and colleagues wrote. “Careful monitoring is required if therapy is initiated. Prospective safety trials are urgently needed.”1

References

1. Alshdifat E, D’Aza D, Yousef H, et al. Safety of GLP-1 and GIP/GLP-1 Agonists in Patients With Prior Alcohol-Related Pancreatitis: A Multi-Center Real-World Cohort Study. Abstract presented at the American Association of Clinical Endocrinology Annual Meeting 2026, Las Vegas, NV. April 22-24, 2026.

2. Ayoub M, Chela H, Amin N, et al. Pancreatitis Risk Associated with GLP-1 Receptor Agonists, Considered as a Single Class, in a Comorbidity-Free Subgroup of Type 2 Diabetes Patients in the United States: A Propensity Score-Matched Analysis. J Clin Med. 2025;14(3):944. Published 2025 Feb 1. doi:10.3390/jcm14030944