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Diabetes and Cancer

Do GLP-1–Based Therapies Increase Cancer Risk?

  1. Michael A. Nauck, MD1⇑ and
  2. Nele Friedrich, PHD2
  1. 1Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Harz, Germany
  2. 2Department of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany
  1. Corresponding author: Michael A. Nauck, michael.nauck{at}diabeteszentrum.de.
Diabetes Care 2013 Aug; 36(Supplement 2): S245-S252. https://doi.org/10.2337/dcS13-2004
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    Figure 1

    Odds ratio and 95% CIs for chronic pancreatitis in studies examining the risk of pancreatitis in patients with type 2 diabetes receiving treatment with the GLP-1 receptor agonist exenatide (A) or the DPP-4 inhibitor sitagliptin (B) relative to other glucose-lowering medications. Analysis of claims databases capturing both prescriptions of specific medications and (hospitalization due to) acute pancreatitis. Data depicted in this figure have been taken from refs. 21–26.

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    Figure 2

    Schematic representation of thyroid C cells, their equipment with GLP-1 receptors, and physiological responses to stimulation with GLP-1 or GLP-1 receptor agonists like exenatide and liraglutide comparing rodent (A) and human (B) C cells. While rodent C cells respond to GLP-1 receptor stimulation with cAMP production, calcitonin release, and proliferative responses (giving rise to hyperplasia, adenomas, or even medullary carcinomas), human C cells express GLP-1 receptors at much lower levels, do not increase cAMP levels, and do not secrete calcitonin in response to GLP-1 receptors even upon long-term stimulation (exposure to GLP-1 receptor agonists in clinical trials lasting up to 1 year).

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    Figure 3

    Odds ratios (95% CI) for reporting pancreatitis, pancreatic carcinoma, thyroid carcinoma, and other/all malignancies in patients with type 2 diabetes prescribed exenatide (green bars) or sitagliptin (blue bars) relative to those taking control diabetes medications, taking into account the frequency of reporting control events (back pain, chest pain, cough, syncope, and urinary tract infection) based on data retrieved from the FDA Adverse Event Reporting System (A), as described by Elashoff et al. (3), for the period from the first quarter, 2004, to the third quarter, 2009. In our confirmatory analysis (B), we used broader search terms for pancreatitis (acute and chronic pancreatitis, pancreatic insufficiency, pancreatic pseudocysts, pancreatic duct stenosis, pancreatic calcifications, pancreatolithisasis, and elevated or abnormal lipase and/or amylase) and used all sulfonylureas as control medications. In the elaborate analysis (C), we included data from the second quarter of 2005 to the fourth quarter of 2010, used broader search terms regarding control events, and included pioglitazone, all sulfonylureas, metformin, and any insulin treatment in the control medications. Numbers indicate case subjects with this diagnosis retrieved from the dataset.

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    Figure 4

    Number of subjects with reports (A) and number of adverse events (B) reported to the FDA Adverse Event Reporting System between 2004 and 2010 for different glucose-lowering medications including exenatide (green lines) and sitagliptin (blue lines). Obviously, in the case of exenatide there was an initial peak, probably related to the fact that this was the first drug in the new class of GLP-1 receptor agonists, and after a nadir in the last quarter of 2007 there was renewed interest, probably as the consequence of initial reports linking exenatide to cases of pancreatitis (1). With sitagliptin, a similar pattern was observed at a lower level.

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Diabetes Care: 36 (Supplement 2)

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August 2013, 36(Supplement 2)
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Do GLP-1–Based Therapies Increase Cancer Risk?
Michael A. Nauck, Nele Friedrich
Diabetes Care Aug 2013, 36 (Supplement 2) S245-S252; DOI: 10.2337/dcS13-2004

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Do GLP-1–Based Therapies Increase Cancer Risk?
Michael A. Nauck, Nele Friedrich
Diabetes Care Aug 2013, 36 (Supplement 2) S245-S252; DOI: 10.2337/dcS13-2004
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  • Epidemiology and Molecular Mechanisms Tying Obesity, Diabetes, and the Metabolic Syndrome With Cancer
  • Insulin Therapy and Cancer
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