An analysis of MedWatch adverse event reports submitted to the Food and Drug Administration in the first two years following approval
- Executive Summary
- Part 1: Background
- Part 2: Methods
- Part 3: Results
- Part 4: Discussion
- Part 5: Conclusion
- Appendix: Charts & Graphs
Background: There have been conflicting reports concerning the pancreatic adverse effects of the incretin mimetic drug class of diabetes medications, with some studies suggesting a link between the drugs and acute pancreatitis. The present study applies objective criteria to the clinical information contained in Food and Drug Administration (FDA) MedWatch adverse event reports to determine the likelihood that the incretin mimetic drug liraglutide causes acute pancreatitis.
Methods: We requested the individual MedWatch case report forms from the FDA for all cases of “pancreatitis acute” associated with liraglutide in the FDA’s Adverse Event Reporting System that were reported to the agency between February 1, 2010, and December 31, 2011, roughly the first two years after liraglutide’s approval. Two researchers independently graded the cases for a causal link using the Naranjo adverse drug reaction probability criteria.
Results: There were 278 unique case reports of acute pancreatitis during liraglutide therapy. Pancreatitis occurred relatively soon after initiating therapy: 30% within one month and 72% within four months. Most cases (60%) required hospitalization. There were three deaths, two from complications of acute pancreatitis. Using the Naranjo criteria, we classified liraglutide as the “probable” causative agent in 51 cases, including 12 for which we deemed a causal link to be highly probable. There was one positive rechallenge, which was classified as a “definite” case of liraglutide-induced acute pancreatitis according to the Naranjo criteria.
Conclusions: Applying the Naranjo causality criteria to FDA MedWatch adverse event reports showed that liraglutide was a “probable” cause of 51 cases of acute pancreatitis as well as a “definite” cause of one case, the latter being the first documented report of a positive rechallenge. These results suggest a causal link between liraglutide and the occurrence of acute pancreatitis.
Next Page » Part I: Background