EditorialGLP-1–Based Therapies: The Dilemma of Uncertainty
Section snippets
Risk of Pancreatitis
Acute pancreatitis accompanying exenatide was first reported in 2006.3 The FDA drew attention to a potential pancreatitis risk associated with sitagliptin in 2009.4 Existing human studies on pancreatitis and incretin-based therapy are conflicting. Two recent analyses involving either exenatide or sitagliptin treatment compared these treatments with other anti-diabetic drug regimen. No relationship between GLP-1 therapy and pancreatitis was reported.5, 6 Notably, Amylin Pharmaceuticals sponsored
Risk of Pancreatic Cancer
Besides an unexpectedly high number of pancreatitis, Elashoff et al report on pancreatic cancer in patients having been treated with exenatide or sitagliptin. Although no clinical study has been performed addressing this issue, the results are in line with a recent analysis of spontaneous reports from Germany performed by the Drug Commission of the German Medical Association. In the German database 11 reports of pancreatic cancer in association with exenatide were identified,12 which was an
Risk of Thyroid Cancer
Liraglutide was associated with medullary thyroid cancer in rodents.17 Despite those findings, liraglutide was approved considering data that suggested a non-genotoxic mechanism and also indicated that the GLP-1R expression in rodent thyroid C cells is higher than in human cells. Marketing approval was given, and linked to specific postmarketing surveillance activities to address this question. The link between exenatide and thyroid cancer presented by Elashoff et al raises some concern.
Acknowledgment
The authors thank Friedrich Luft for his thoughtful comments.
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2016, International Review of Cell and Molecular BiologyCitation Excerpt :Chronic pancreatitis has been shown to increase the risk of pancreatic cancer 26-fold (Lowenfels et al., 1993). Both FDA and German regulatory databases indicate signs for development of pancreatic cancer for exenatide and FDA database for sitagliptin (Elashoff et al., 2011; Spranger et al., 2011). There were 258 pancreatic cancers reported for exenatide, 63 for liragluitide, 81 for sitagliptin, 18 for saxagliptin, and 1 for linagliptin.
Should GLP-1 receptor agonists be used with caution in high risk population for colorectal cancer?
2014, Medical HypothesesCitation Excerpt :Based on their findings, Meike Körner and colleagues suggested that the GLP-1 receptors may represent a novel molecular target for in vivo scintigraphy and targeted radiotherapy for a variety of GLP-1 receptor-expressing tumors [18]. And there is a signal for pancreatic cancer for exenatide in German regulatory databases and for sitagliptin in the FDA database [19,20]. The signal has grown stronger with 258 pancreatic cancers for exenatide, 63 for liraglutide, 81 for sitagliptin, 18 for saxagliptin, and 1 for linagliptin [21].
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2014, Progress in Molecular Biology and Translational ScienceCitation Excerpt :Thus, the nature of the adaptive change that underlies remission of T2DM after gastric bypass surgery remains to be determined. An ongoing controversy concerns whether the use of GLP-1-based therapeutics predisposes to unexpected side effects including inflammation of the pancreas (pancreatitis) or even pancreatic cancer in patients with T2DM.270–274 Furthermore, postmortem histological analyses of pancreatic tissue from patients treated with a GLP-1R agonist or DPP-IV inhibitors provide evidence for an increased incidence of pancreatic exocrine cell dysplasia accompanied by hyperplasia of glucagon-secreting α-cells of the endocrine pancreas.79
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Conflict of interest The authors disclose the following: Joachim Spranger has lectured for or received consultant honorary from Eli Lilly, NovoNordisk, Berlin Chemie, Merck-Sharp & Dohme, Bristol-Myers Squibb, Novartis, Takeda, GlaxoSmithKline and Sanofi-Aventis. The remaining authors disclose no conflicts.