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Diabetes Obes Metab. 2016 Dec;18(12):1253-1262. doi: 10.1111/dom.12766. Epub 2016 Sep 26.

Histological changes in endocrine and exocrine pancreatic tissue from patients exposed to incretin-based therapies.

Author information

Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
Department of Pathology, Ruhr-University Bochum, Bochum, Germany.
Department of Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
Bellvitge Hospital, Department of Endocrinology, Feixa Llarga s/n, Hospitalet de Llobregat, 08907, Barcelona, Spain.

Erratum in



Incretin-based therapies have been associated with an increased risk of pancreatitis. Recently, various histological abnormalities have been reported in human pancreatic tissue from brain-dead organ donors who had been exposed to incretin-based drugs. In the present study we examined pancreatic tissue collected at surgery.


Human pancreatic tissue from 7 type 2-diabetic patients treated with incretin-based drugs (type 2-I), 6 diabetic patients without incretin treatment (type 2-NI), 11 patients without diabetes (no diabetes group) and 9 brain-dead organ donors (BDOD group) was examined.


Fractional beta-cell area was reduced in the type 2-NI group compared to the group without diabetes (P < .05), but there was no difference compared to the type 2-I patients. Alpha-cell area (P = .30), beta-cell replication (P = .17) and alpha-cell replication (P = .91) were not different. There were also no differences in acinar cell (P = .13) and duct cell replication (P = .099). Insulin-positive duct cells were more frequent in the type 2-I and the BDOD groups (P = .034). No co-expression of insulin and glucagon was detected. Pancreatic intraepithelial neoplasia (PanIN) lesions were very rare, all low-grade (PanIN 1a and 1b) and tended to occur more frequently in the type 2-I group (P = .084).


The present results did not reveal marked histological abnormalities in the pancreas of incretin-treated patients with type 2 diabetes. Low numbers of specimens available and a large inter-individual variability of the findings warrant caution regarding the interpretation of histological data concerning drug effects on the human pancreas.


DPP-4 inhibitors; GLP-1; GLP-1 analogues; pancreatic cancer; pancreatitis

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