GLP-1 drugs associated with hospitalizations for pancreatitis

Sitagliptin and exenatide were associated with increased risk of hospitalization for acute pancreatitis, according to a recent study of patients with type 2 diabetes.

The population-based, case-control study used an administrative database to identify 1,269 patients with type 2 diabetes who were hospitalized with acute pancreatitis between 2005 and 2008. They were matched to 1,269 control subjects based on age, sex, enrollment pattern and diabetes complications. The study was published online by JAMA Internal Medicine on Feb. 25.

After adjustment for confounders, including metformin use, the study found that patients who had taken one of these glucagonlike peptide-1 (GLP-1)-based therapies in the prior 30 days were significantly more likely to be hospitalized with acute pancreatitis (adjusted odds ratio [AOR], 2.24; 95% CI, 1.36 to 3.68). Taking the drugs more than 30 days but less than two years prior was also associated with increased risk (AOR, 2.01; 95% CI, 1.37 to 3.18). The study also found a number of other factors more common in GLP-1 patients than controls, including hypertriglyceridemia, alcohol use, gallstones, tobacco use, obesity, biliary and pancreatic cancer, cystic fibrosis and any neoplasm.

The study authors concluded that sitagliptin and exenatide were associated with increased odds of hospitalization for acute pancreatitis. They noted that this finding supports previous mechanistic studies and reports to the FDA, although overall the evidence on GLP-1 drugs and pancreatitis is mixed. This study was limited by the possibility of additional confounders and the exclusion of patients over age 64. In addition, data on the long-term risk of pancreatic cancer and newer GLP-1-based therapies were not available.

The authors called for future studies to clarify the findings, particularly whether patients with certain genetic mutations or pancreatic risks, such as obesity, are at elevated risk. Another open research question is whether monitoring of serum enzyme levels might predict acute pancreatitis in patients on GLP-1 drugs.