Incretin-mimetic therapies and pancreatic disease: a review of observational data

Abstract

Background/objective:

Signals from the FDA Adverse Event Reporting System (AERS) and pre-clinical and human pancreata obtained from organ donors have suggested that incretin-based therapies used to treat type 2 diabetes mellitus, such as glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, may increase the risk of acute pancreatitis (AP) and pancreatic cancer (PC). However, data from observational studies and randomized trials have been conflicting. We conducted a literature review to identify and summarize all observational data published assessing the pancreatic safety of incretins.

Methods:

Searches were conducted in MEDLINE via PubMed and Embase using the key terms for the time period of 1 January 2005, to 12 February 2014. A total of 180 articles were screened in abstract form and 49 were subsequently reviewed in full text for inclusion. Data from 12 articles are included in this report.

Findings:

Data from the FDA AERS database suggest increased risk of AP and PC with GLP-1 receptor agonist and DPP-4 inhibitor use. These findings are not supported by population-based observational studies for either AP or PC; however, studies assessing the relationship between PC and incretin-based therapies are limited.

Conclusions:

Current evidence is conflicting and inadequate to conclude whether use of incretin-based therapies increases the risk of AP and PC. Further studies, with the ability to provide long term follow-up, are needed.

Keywords::

• Acute pancreatitis
• Incretin therapies
• Pancreatic cancer
• Type 2 diabetes

Transparency

Declaration of funding

This study was funded by GlaxoSmithKline.

Declaration of financial/other relationships

C.E.K., J.C., and S.A. have disclosed that they are employees of GlaxoSmithKline, a pharmaceutical company that manufactures and markets medications for the treatment of type 2 diabetes, and currently own shares of company stock. A.A. has disclosed that he is an employee of Eli Lilly and Company as of 2 January 2014. A.S. has disclosed that she is an employee of PatientsLikeMe as of 3 March 2014. This work was completed while A.A. and A.S. were employed at New England Research Institutes Inc. E.S. has disclosed that she has no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.