Januvia Causes Precancerous Changes in Transgenic Rats with Human Pancreas Cells

Page Changed: Januvia

A study published in July 2009 found evidence that while Januvia improved pancreatic beta cell function in the short term, it did so while producing pre-cancerous changes in the pancreatic duct cells.

You can read the abstract of this study here:

Beneficial Endocrine but Adverse Exocrine Effects of Sitagliptin in the Human Islet Amyloid Polypeptide Transgenic Rat Model of Type 2 Diabetes: Interactions With Metformin Aleksey V. Matveyenko et al. Diabetes. doi: 10.2337/db09-0058 Diabetes July 2009 vol. 58 no. 7 1604-1615

This study was conducted in human islet amyloid polypeptide transgenic (HIP) rats which have had human genes inserted into their pancreata. The HIP rats were treated with Januvia, or metformin, the combination of sitagliptin plus metformin, or no drug as controls for 12 weeks.

It found that "Metformin more than sitagliptin [Januvia] inhibited ß-cell apoptosis [cell death]. Metformin enhanced hepatic insulin sensitivity;"

But when Januvia was added to the mix, there was a small improvement in insulin sensitivity and in beta cell function. Note that "beta cell function" is only a measure of insulin secretion. It is not a sign that more beta cells are growing, only that existing beta cells are pumping out more insulin.

In fact, the finding, reported above was that beta cells survived better in the transgenic rats given metformin alone compared to those given Januvia.

But any benefit that might have come from increased insulin secretion was cancelled out by a very troubling finding. Here is the way the researchers report it:

sitagliptin enhanced extrahepatic insulin sensitivity with a synergistic effect in combination. ß-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 [emphasis mine].

"Metaplasia" is defined this way in Mosby's Medical Dictionary, 8th edition. © 2009, Elsevier:

the reversible conversion of normal tissue cells into another, less differentiated cell type in response to chronic stress or injury. With prolonged exposure to the inducing stimulus, cancerous transformation can occur.