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Diabetes. 2009 Jul;58(7):1604-15. doi: 10.2337/db09-0058. Epub 2009 Apr 29.

Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin.

Author information

1
Larry Hillblom Islet Research Center, Division of Endocrinology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. amatveyenko@mednet.ucla.ed

Abstract

OBJECTIVE:

We sought to establish the extent and mechanisms by which sitagliptin and metformin singly and in combination modify islet disease progression in human islet amyloid polypeptide transgenic (HIP) rats, a model for type 2 diabetes.

RESEARCH DESIGN AND METHODS:

HIP rats were treated with sitagliptin, metformin, sitagliptin plus metformin, or no drug as controls for 12 weeks. Fasting blood glucose, insulin sensitivity, and beta-cell mass, function, and turnover were measured in each group.

RESULTS:

Sitagliptin plus metformin had synergistic effects to preserve beta-cell mass in HIP rats. Metformin more than sitagliptin inhibited beta-cell apoptosis. Metformin enhanced hepatic insulin sensitivity; sitagliptin enhanced extrahepatic insulin sensitivity with a synergistic effect in combination. beta-Cell function was partially preserved by sitagliptin plus metformin. However, sitagliptin treatment was associated with increased pancreatic ductal turnover, ductal metaplasia, and, in one rat, pancreatitis.

CONCLUSIONS:

The combination of metformin and sitagliptin had synergistic actions to preserve beta-cell mass and function and enhance insulin sensitivity in the HIP rat model of type 2 diabetes. However, adverse actions of sitagliptin treatment on exocrine pancreas raise concerns that require further evaluation.

PMID:
19403868
PMCID:
PMC2699878
DOI:
10.2337/db09-0058
[Indexed for MEDLINE]
Free PMC Article

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