Are incretin mimetics and enhancers linked to pancreatitis and malignant transformations in pancreas?

Abstract

Introduction: Dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists are new options in the treatment of type 2 diabetes mellitus. However, due to accumulating reports on the occurrence of acute pancreatitis (AP), a suspicion of an association between incretin-based therapies and pancreatic disease has arisen.

Areas covered: A review of the literature on the safety of incretin-based therapies in regard to AP and pancreatic cancer was undertaken with discussion of potential mechanisms as well as limitations.

Expert opinion: Until now, several preclinical and clinical studies have been published; however, they present conflicting results. Common risk factors, low incidence rates, long latency periods (in regard to pancreatic malignancy), lack of availability of human pancreatic tissues during lifetime among others hamper the confirmation or exclusion of a causal association. The results of the ongoing large randomized controlled trials will add further data. In line with current recommendations by European Medicines Agency and FDA, incretin-based therapies should be discontinued in patients with suspicion of AP, and incretin mimetics should not be administered to patients with a history of AP. However, based on current knowledge, there is no sound reason for depriving type 2 diabetic patients in general of a beneficial and effective therapy. However, this conclusion cannot be final and should be subject to constant reevaluation and, if necessary, change.

Keywords: dipeptidyl peptidase-4 inhibitor; gliptins; glucagon-like peptide-1; insulin; obesity; pancreatic cancer; pancreatitis; type 2 diabetes mellitus.