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

Abstract

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.

Keywords:

• cancer risk
• GLP-1 receptor agonists
• incretin-based therapy
• side effects

Declaration of interest

A Consoli has received honorary for participation in advisory board and/or speaker fee from Astra Zeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Ely Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi- Aventis and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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