In This Issue of Diabetes
Edited by Helaine E. Resnick, PhD, MPH
Incretin-Based Therapies: Are They Safe?
New work by Butler et al. shows increased β-cell and α-cell mass resulting from incretin therapy in type 2 diabetes mellitus (DM). A deficit in β-cell mass is one characteristic of DM. One class of drugs for treating DM, the glucagon-like peptide-1 (GLP-1) mimetic drugs known as incretins, has been shown to induce β-cell regeneration in rodents. However, it is unknown whether GLP-1 has the same property in adult humans, and there is a concern that GLP-1 might cause an unwanted expansion of the exocrine pancreas. In this issue of Diabetes (p. 2595), Butler et al. analyzed 34 human pancreata from brain-dead organ donors with and without DM. Eight of the donors with DM had undergone incretin therapy (seven treated with sitagliptin and one with exenatide). In the DM group that had not undergone incretin therapy (12 individuals), the investigators reported a 60% deficit in β-cell mass with no change in α-cell mass compared with individuals without diabetes (14 individuals). Individuals treated with incretins showed a significant expansion of the exocrine and endocrine pancreatic compartments. The investigators believe this may suggest an increased risk of neuroendocrine tumors as a result of GLP-1 therapy. An accompanying commentary on p. 2178 by Steven E. Kahn, MB, ChB, however, underscores the need for further research before conclusions are drawn regarding the safety of incretin therapy. Kahn points out several differences between the study group and the control group, and cautions that these differences, as well as other considerations, could have a substantial impact on interpretation …