A meta-analysis of serious adverse events reported with exenatide and liraglutide: Acute pancreatitis and cancer

Alves, Carlos; Marques, Francisco Batel; Macedo, Ana

doi:10.1016/j.diabres.2012.09.008

Cited by 138 publications

(100 citation statements)

References 27 publications

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“…At least 11 case reports suggested a relationship between liraglutide and pancreatitis, highlighting pancreatitis as a potential complication of therapy and suggesting caution when prescribing liraglutide (17). Meanwhile, a meta-analysis of 25 longitudinal studies ( (20). More recently, a liraglutide audit conducted by the Association of British Clinical Diabetologists reported that after 3,720 years of exposure to liraglutide across 6,010 patients, four cases of possible pancreatitis were documented.…”

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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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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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“…Dose-dependent detrimental effects concerning liraglutide have been reported, such as the induction of a high risk of pancreatic and thyroid cancer in rats (61)(62)(63). Our present work showing impaired liraglutide binding in diabetics raises the need for further research to prevent glycationmediated alterations of albumin-drug binding capacity.…”

Section: Discussionmentioning

confidence: 78%

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

Soudahome

Catan

Giraud

et al. 2018

Journal of Biological Chemistry

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“…In contrast to the above results, several recent studies and meta-analyses failed to show increased risk of pancreatitis with the use of GLP-1 receptor agonists [72][73][74][75][76][77][78][79][80][81][82]. A meta-analysis of 55 randomized controlled trials (n = 33,350) showed no increased risk of pancreatitis with GLP-1 agonists compared with controls (OR: 1.05, 95% CI: 0.37-2.94) [83].…”

Section: Pancreasmentioning

confidence: 72%

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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A meta-analysis of serious adverse events reported with exenatide and liraglutide: Acute pancreatitis and cancer

Cited by 138 publications

References 27 publications

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

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

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

Adverse Effects of GLP-1 Receptor Agonists

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