Potential side effects to GLP-1 agonists: understanding their safety and tolerability

Introduction: Glucagon-like peptide 1 receptor (GLP-1Rx) agonists might elicit unwelcome side effects and concerns have recently been raised about their safety. Areas covered: Available evidence about safety, tolerability and potential adverse events relative to GLP-1Rx agonists presently used. We searched the MEDLINE database using the terms: 'GLP-1 receptor agonists', 'Incretin therapy side effects', 'exenatide', 'liraglutide', 'exenatide long-acting release', ' lixisenatide'. Articles were selected on the basis of the study design and importance, in the light of authors' clinical experience and personal judgment. The main safety concern about GLP-1Rx agonists use is the possible association with increased risk of pancreatitis and/or tumors. This concern stems mainly from limited observations in animal models not confirmed in similar studies. Furthermore, clinical studies reporting association between GLP-1Rx agonist use and pancreatitis/cancer are marred by several biases and both clinical trials and post-marketing analyses failed to demonstrate a significant association. Expert opinion: As stated by both FDA and EMA, the safety concerns emerged so far about GLP-1RX agonists should not affect present prescribing habits. Thus, although a strict data monitoring must be encouraged, they should not prevent access to the benefits of an innovative treatment, such as GLP-1Rx agonists use, to a large diabetic population still confronted with unmet needs.