Association of pancreatitis with glucagon-like peptide-1 agonist use.
OBJECTIVE
To review the possible association between glucagon-like peptide-1 (GLP-1) agonist use and pancreatitis in patients with type 2 diabetes mellitus.


METHODS
A MEDLINE search (1950-January 2010) identified key clinical trials delineating adverse effects associated with GLP-1 agonist use. Key search terms included type 2 diabetes mellitus, pancreatitis, incretins, exenatide, liraglutide, albiglutide, and taspoglutide. Review of references listed in the articles identified was also performed. The Food and Drug Administration (FDA) Web site and Amylin Pharmaceuticals file data were utilized to extract case report information and unpublished clinical development data related to GLP-1 agonist use and pancreatitis.


METHODS
Phase 2 and 3 clinical trials evaluating exenatide, liraglutide, albiglutide, and taspoglutide that discussed treatmentrelated adverse effects as well as FDA-reviewed case reports of pancreatitis in patients taking these same therapies were included. One study evaluating type 2 diabetes as a risk factor for development of acute pancreatitis was also included. Exenatide case reports and clinical development data were also included.


RESULTS
Currently there have been 8 cases during clinical development and 36 postmarketing reports of acute pancreatitis in exenatide-treated patients. Four patients have developed acute (n = 3) or chronic (1) pancreatitis during liraglutide clinical trials. There have been no reports to date of development of acute pancreatitis in patients taking albiglutide or taspoglutide.


CONCLUSIONS
Observational reports and clinical trial data suggest an association between GLP-1 agonist use and acute pancreatitis; however, additional clinical trial data and in-depth case report analysis are needed to further evaluate and verify this finding.
Anderson
Sarah L
SL
School of Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA. sarah.anderson@ucdenver.edu
Trujillo
Jennifer M
JM
D000208:Acute Disease; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D010195:Pancreatitis / Q000139:chemically induced* / Q000150:complications
D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1