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Popular Diabetes Drugs May Cause Abnormal Pancreatic Growth

First report of precancerous changes in humans (Mar. 26)

Patients who had taken a type of drug commonly used to treat type 2 diabetes showed abnormalities in the pancreas, including cell proliferation, that may be associated with an increased risk of neuroendocrine tumors, according to a new study by researchers at the University of California, Los Angeles and at the University of Florida. Their findings were published online in Diabetes.

The investigators found that cell mass was increased approximately 40% in the pancreases of deceased organ donors who had type 2 diabetes and who had been treated with incretin therapy. This popular type of treatment uses the action of a gut hormone, glucagon-like peptide 1 (GLP-1), to lower blood sugar in the body.

Although there have been conflicting reports on the effects of the incretin class of drugs on the pancreas in animal studies, this is the first study to note such changes in the human pancreas.

The researchers examined the pancreases of 20 deceased organ donors with type 2 diabetes. Eight donors had been treated for at least 1 year with incretin therapy, while the other 12 had received therapies that didn’t include incretin-based drugs. The researchers also evaluated 14 pancreases from a control group of nondiabetic individuals of similar age.

The pancreases of the individuals who had received incretin therapy were larger than those of patients treated with 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 produce the hormone glucagon).

The latter finding likely resulted from the ability of GLP-1–based therapies to suppress the release of glucagon by alpha cells, since decreasing the availability or action of the hormone glucagon has been shown to induce the 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 had a neuroendocrine tumor composed of alpha cells.

Of the eight donors who were on incretin therapy, seven had been taking sitagliptin (Januvia, Merck), and one had been taking exenatide (Byetta, Bristol-Myers Squibb). These and similar drugs are currently under investigation by the FDA for their possible links to pancreatitis and pancreatic cancer.

Source: UCLA; March 26, 2013.

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