The gastrointestinal safety of incretin-based therapies is controversial. Two new studies find no effect of GLP-1 receptor agonists on acute pancreatitis risk, but increased risk of bile duct and gallbladder disease. However, no retrospective epidemiological studies can provide definitive answers, and nausea, vomiting and diarrhoea remain the most clinically relevant adverse effects of these drugs, compromising long-term adherence.
This is a preview of subscription content, log in via an institution to check access.
References
Meier, J. J. & Nauck, M. A. Risk of pancreatitis in patients treated with incretin-based therapies. Diabetologia 57, 1320–1324 (2014).
Gale, E. A. M. Smoke or fire? Acute pancreatitis and the liraglutide trials. Diabetes Care 38, 948–950 (2015).
Abbas, A. S., Dehbi, H. M. & Ray, K. K. Cardiovascular and non-cardiovascular safety of dipeptidyl peptidase-4 inhibition: a meta-analysis of randomized controlled cardiovascular outcome trials. Diabetes Obes. Metab. 18, 295–299 (2016).
Azoulay, L. et al. Association between incretin-based drugs and the risk of acute pancreatitis. JAMA Intern. Med. http://dx.doi.org/10.1001/jamainternmed.2016.1522 (2016).
Faillie, J. L. et al. Association of bile duct and gallbladder diseases with the use of incretin-based drugs in patients with type 2 diabetes mellitus. JAMA Intern. Med. http://dx.doi.org/10.1001/jamainternmed.2016.1531 (2016).
Meier, J. J. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat. Rev. Endocrinol. 8, 728–742 (2012).
Rosenstock, J. et al. Efficacy and safety of lixilan, a titratable fixed-ratio combination of lixisenatide and insulin glargine, versus insulin glargine in type 2 diabetes inadequately controlled on metformin monotherapy: the LixiLan proof-of-concept randomized trial. Diabetes Care 39, 1579–1586 (2016).
Azoulay, L. Incretin-based drugs and adverse pancreatic events: almost a decade later and uncertainty remains. Diabetes Care 38, 951–953 (2015).
Davies, M. J. et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA 314, 687–699 (2015).
Marso, S. P. et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375, 311–322 (2016).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
J.R. has served on scientific advisory boards and received honorarium or consulting fees from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Intarcia, Janssen, Merck, Novo Nordisk and Sanofi. He has received grants and/or research support from Asahi, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Hanmi, Intarcia, Janssen, Lexicon, MannKind, Merck, Novo Nordisk, Pfizer, Sanofi and Takeda. J.J.M. has received consulting and speaker honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novo Nordisk and Sanofi. He has received research support from Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Novo Nordisk and Sanofi.
Supplementary information
Supplementary information S1 (table)
Practical recommendations for the use of GLP-1 receptor agonists in patients with gastrointestinal diseases (PDF 87 kb)
PowerPoint slides
Rights and permissions
About this article
Cite this article
Meier, J., Rosenstock, J. Gastrointestinal safety of incretin therapies: are we there yet?. Nat Rev Gastroenterol Hepatol 13, 630–632 (2016). https://doi.org/10.1038/nrgastro.2016.149
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrgastro.2016.149
- Springer Nature Limited