Elevated amylase and lipase levels in patients using glucagonlike peptide-1 receptor agonists or dipeptidyl-peptidase-4 inhibitors in the outpatient setting.

OBJECTIVE: To investigate the effects of glucagonlike peptidase-1 (GLP-1) receptor agonists and dipeptidyl-peptidase-4 (DPP-4) inhibitors on serum amylase and serum lipase levels in patients with type 2 diabetes.
METHODS: In 90 patients with type 2 diabetes, treatment was initiated with a GLP-1 agonist or a DPP-4 inhibitor. A comparison group consisted of 33 patients with type 2 diabetes and similar characteristics who were not prescribed these agents. Baseline serum amylase and lipase levels were measured in all patients and repeated periodically. We determined the percentage of patients with elevated levels of serum amylase or lipase (or both) in both groups.
RESULTS: Among all 90 patients who received a GLP-1 receptor agonist or a DPP-4 inhibitor, 32 (36%) had an increase in serum amylase or lipase (or both) in comparison with 6 of 33 patients (18%) with such increases in the comparison group. Interestingly, the serum lipase levels increased more than the serum amylase values in all groups. To ascertain that this was not a chance laboratory error, serum samples were submitted to a second independent laboratory, and the same results were obtained. Usually, use of the medication was discontinued when serum lipase or amylase values were found to be elevated at any level.
CONCLUSION: Both GLP-1 receptor agonists and DPP-4 inhibitors are associated with increased levels of serum lipase more than serum amylase in many patients with type 2 diabetes, possibly suggesting the presence of pancreatic inflammation. Whether this finding may potentially lead to acute pancreatitis or chronic pancreatitis, as reported in rat models, is currently unknown. Careful observation of patients taking these medications may be prudent.