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Research suggests popular diabetes drugs can cause abnormal pancreatic growth in humans
Date:3/27/2013

e other 12 had received therapies that didn't include incretin-based drugs. The researchers also evaluated 14 pancreases from a control group of non-diabetic individuals of similar age.

The pancreases of the individuals who had been on incretin therapy were larger than those of patients on other types of diabetes therapies, and this larger size was associated with increased cellular proliferation. Incretin-treated individuals showed an increase in pancreas dysplasia, an abnormal form of cell proliferation that is a risk factor for pancreatic cancer, as well as an expansion of alpha cells, endocrine cells that make the hormone glucagon.

This latter finding is likely a consequence of GLP-1based therapies' suppression of the release of glucagon by alpha cells, since decreasing the availability or action of the hormone glucagon has been shown in a variety of prior studies to induce a proliferation of pancreatic alpha cells. This alpha-cell expansion has been associated with the development of pancreatic neuroendocrine tumors. Three of the eight incretin-treated individuals had microadenomas and one has a neuroendocrine tumor composed of alpha cells.

Of the eight donors who were on incretin therapy, seven had been taking sitagliptin, sold in pill form as Januvia and marketed by Merck, and one had been on exenatide, sold as Byetta by Bristol-Myers Squibb. These and similar drugs are currently under investigation by the U.S. Food and Drug Administration for their possible links to pancreatitis and pancreatic cancer.

"These findings lend additional weight to concerns regarding the effects of long term GLP-1related therapy, with respect to both unintended proliferative actions on the exocrine pancreas and now also a possible increased risk of neuroendocrine tumors," the researchers write. "In addition to the surveillance previously recommended for the potential association of GLP-1 based therapy and pancreatic cancer risk, the curr
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Contact: Enrique Rivero
erivero@mednet.ucla.edu
310-794-2273
University of California - Los Angeles Health Sciences
Source:Eurekalert

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