Comment on: Butler et al. Marked Expansion of Exocrine and Endocrine Pancreas With Incretin Therapy in Humans With Increased Exocrine Pancreas Dysplasia and the Potential for Glucagon-Producing Neuroendocrine Tumors. Diabetes 2013;62:2595–2604

  1. David E. Moller
  1. Lilly Research Laboratories and Lilly Diabetes, Eli Lilly & Co., Indianapolis, Indiana.
  1. Corresponding author: David E. Moller, mollerda{at}

In the July issue of Diabetes, Butler et al. (1) described histopathologic findings of potential concern in pancreatic tissue obtained at time of death from 8 patients who were reportedly treated with “incretin” -based therapies (sitagliptin or exenatide). A small number of pancreata from diabetes patients and nondiabetic subjects served as controls. We acknowledge the importance of questions that pertain to human safety with newer glucose-lowering agents, and we appreciate the difficult and labor-intensive nature of this study (1). There are several limitations of the reported work that warrant comment.

Firstly, the number of pancreas samples examined was very small; from 7 sitagliptin-treated patients and 1 exenatide-treated patient. A number of demographic characteristics, which might be critical to the analysis, were different between incretin-treated and control subjects. One-half of the control diabetes patients had a short duration of disease (<5 years) versus only 1 of 8 of the incretin patients; the severity of disease was also clearly different—5 of 12 control diabetes patients were receiving no antihyperglycemic therapy. The 8 incretin-treated patients were also significantly older (∼18 …

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