Risk of pancreatitis in patients treated with incretin-based therapies

Meier, Juris J.; Nauck, Michael A.

doi:10.1007/s00125-014-3231-y

Cited by 86 publications

(59 citation statements)

References 11 publications

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“…Parts of this study were presented at the 2012 Joint Meeting of the American Pancreatic Association and International Association of Pancreatology, Miami, FL, 31 October-3 November 2012 (49). These data were subsequently incorporated into studies published by other authors (16,24). A short statement on six of the cases included in the case reviews was included in a letter to The Annals of Pharmacotherapy (35).…”

Section: Discussionmentioning

confidence: 99%

Is There a Link Between Liraglutide and Pancreatitis? A Post Hoc Review of Pooled and Patient-Level Data From Completed Liraglutide Type 2 Diabetes Clinical Trials

2015

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OBJECTIVETo report the incidence of pancreatitis in type 2 diabetes trials of liraglutide and details of all pancreatitis cases. RESEARCH DESIGN AND METHODSData from Novo Nordisk-sponsored trials with liraglutide (phase 2 and 3; NN2211 identifiers) completed by 19 April 2013 were pooled. All pancreatitis cases were reviewed. RESULTSTotal exposure to liraglutide and active comparators was 5,021 and 1,354 patientyears, respectively (n = 6,345 and 1,846, respectively). Eight cases of acute pancreatitis (AP) with liraglutide and one with any comparator (glimepiride) were found. The incidence of AP was 1.6 cases/1,000 patient-years exposure (PYE) for liraglutide vs. 0.7 cases/1,000 PYE for total active comparators. One of the eight AP cases reported with liraglutide did not meet diagnostic criteria for AP. In six of these eight cases, recognized risk factors for AP were present and/or the onset of AP occurred >6 months after liraglutide initiation. All patients were receiving multiple medications. Four cases of chronic pancreatitis (CP) with liraglutide and none with comparators were found. One of these four cases fulfilled diagnostic criteria for CP; these criteria were not met or information was missing in the remaining three. CONCLUSIONSBased on the small number of cases observed, the incidences of reported AP and CP were numerically greater with liraglutide than with comparators. Not all cases fulfilled diagnostic criteria, and confounding variables were present in 75% of the AP cases with liraglutide therapy, precluding firm conclusions.In 2007, the U.S. Food and Drug Administration (FDA) prompted an update of the exenatide twice daily label to include a warning for acute pancreatitis (1). This update was based on six acute pancreatitis cases in patients receiving exenatide twice daily in clinical trials together with several postmarketing case reports (1); 1 UK Medical Affairs, Novo Nordisk Ltd., Gatwick, U.K. A slide set summarizing this article is available online.

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Section: Discussionmentioning

confidence: 99%

Is There a Link Between Liraglutide and Pancreatitis? A Post Hoc Review of Pooled and Patient-Level Data From Completed Liraglutide Type 2 Diabetes Clinical Trials

2015

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“…These factors may lead to an increased risk of pancreatitis in patients treated with GLP-1-based therapies. A pooled analysis of phase III clinical trials and two endpoint trials showed a slightly elevated (but not significant) risk of pancreatitis with GLP-1 receptor agonists (38 events, 17,775 patient-years of exposure) compared with the alternative treatment (nine events, 5,863 patient-years of exposure; OR: 1.39 (95% CI: 0.67-2.88)) [70]. Based on these observations, the US Food and Drug Administration (FDA) investigated the risk of pancreatitis associated with the use of incretin-mimetic drugs [71].…”

Section: Pancreasmentioning

confidence: 99%

Adverse Effects of GLP-1 Receptor Agonists

2014

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■ AbstractGlucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1 receptor agonists are described. The review also provides the reader with structured data that compare the rates of the most common adverse effects for each of the various GLP-1 receptor agonists.

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“…Pooled analyses of studies of GLP-1 receptor agonists exenatide, liraglutide, and lixisenatide suggested a numerically increased incidence of pancreatitis with these drugs, but there were few cases [7,8]. After comprehensive review of data from study drugs in the incretin class from many sponsors, the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have stated that available evidence does not support concern about pancreatic safety with incretin-based thera-…”

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confidence: 99%