Several randomized trials with metabolic outcomes have reported that glucagon like peptide-1 receptor agonists (GLP-1 RA) could be associated with an increased risk of pancreatitis. The present meta-analysis aimed to examine this hypothesis.
An extensive Medline, Embase, and Cochrane Database search for “exenatide”, “liraglutide”, “albiglutide”, “taspoglutide”, “dulaglutide”, “lixisenatide”, and “semaglutide” was performed up to March 31st, 2013. Inclusion criteria: (i) randomized trials, (ii) duration ≥12 weeks; (iii) on type 2 diabetes; and (iv) comparison of GLP-1RA with placebo or active drugs. Mantel–Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for pancreatitis.
80 eligible trials were identified. Of these, 39 had not disclosed their findings or did not report any information on pancreatitis. The remaining 41 trials enrolled 14,972 patients, with a total exposure of 14,333 patient × years (8353 and 5980 patient × years for GLP-1 receptor agonists and comparators, respectively). The overall risk of pancreatitis was not different between GLP-1RA and comparators (MH-OR: 1.01[0.37; 2.76]; p = 0.99).
The present meta-analysis does not suggest any increase in the risk of pancreatitis with the use of GLP-1RA. However, it should be recognized that the number of observed cases of incident pancreatitis is very small and the confidence intervals of risk estimates are wide.
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- Incretin-based therapies: review of current clinical trial data.Am J Med. 2010; 123: S28-S37.2
- Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials.BMJ. 2012; 344: d7771https://doi.org/10.1136/bmj.d7771
- Incretin-based therapies and cardiovascular risk.Curr Med Res Opin. 2012; 28: 715-721
- GLP-1 receptor agonists: a clinical perspective on cardiovascular effects.Diab Vasc Dis Res. 2012; 9: 95-108
- Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials.Exp Diabetes Res. 2011; 2011: 215764
- Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies.Diab Vasc Dis Res. 2011; 8: 237-240
- Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study.JAMA Intern Med. 2013; 173: 534-539
- Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies.Gastroenterology. 2011; 141: 150-156
- Assessing the quality of reports of randomized clinical trials: is blinding necessary?.Control Clin Trials. 1996; 17: 1-12
- Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560
- Operating characteristics of a rank correlation test for publication bias.Biometrics. 1994; 50: 1088-1101
- Bias in meta-analysis detected by a simple, graphical test.BMJ. 1997; 315: 629-634
- Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.Ann Intern Med. 2009; 151 (W64): 264-269
- Incretin-based therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits.Diabetes Care. 2010; 33: 428-433
- Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: a retrospective observational pharmacy claims analysis.Diabetes Care. 2010; 33: 2349-2354
- Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide.Curr Med Res Opin. 2009; 25: 1019-1027
Published online: January 31, 2014
Accepted: January 4, 2014
Received in revised form: May 2, 2013
Received: May 2, 2013
© 2014 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.