Common diabetes drug not linked to short-term risk of pancreatic cancer

"Our research shows that short-term use of DPP-4 inhibitors in older diabetes patients does not increase their risk for pancreatic cancer," said John Buse, MD, PhD, director of the Diabetes Care Center at UNC and co-author of the paper in the current issue of the journal Diabetes, Obesity and Metabolism. "However, we just cannot address the long-term safety, yet. There are just not enough people who have taken the drug for many years."

DPP-4 inhibitors came on the market in 2006. Since then, these drugs have become some of the most commonly prescribed diabetes medications, primarily because they often cause fewer side effects compared to other diabetes treatments.

But in 2009, the Food and Drug Administration issued a safety warning for DPP-4 inhibitors following reports of acute pancreatitis in patients. Subsequent to that warning, analysis of the FDA Adverse Events Reporting database and autopsy studies suggested that patients who had taken DPP-4 inhibitors faced an increased risk of pancreatic cancer. However, other researchers were critical of the studies, saying the research had been limited by study design, small numbers of patients involved, and the absence of key information needed to make the claim that DPP-4 inhibitors were linked to short-term risk of pancreatic cancer.

Using a more advanced study design, UNC researchers led by Mugdha Gokhale, MS, research assistant at UNC Gillings School of Global Public Health, compared the rate of pancreatic cancer diagnoses among a random sample of Medicare beneficiaries. Some patients had taken DPP-4 inhibitors; others had taken two different but also commonly prescribed medications -- sulfonylureas and thiazolidinediones. Then researchers compared the rate of pancreatic cancer diagnoses among the two groups of patients and found no increased risk of pancreatic cancer among patients who had used DPP-4 inhibitors. The study examined real-world treatment patterns and used a variety of well-validated research techniques to minimize confounding problems that can occur in such observational studies.

This population-based study, which mimicked clinical treatment decisions, indicated that cancer risk among older diabetic patients using DPP-4 drugs does not increase even in the second year of drug exposure. However, longer treatment periods have not been studied, nor have long-term risks. But Buse said that the results should reassure patients and providers regarding the safety of DPP-4 inhibitors for older patients.

The UNC study was funded by a pilot award from the North Carolina Translational and Clinical Sciences (NC TraCS) Institute, home of the NIH Clinical and Translational Science Awards (CTSA) Program at UNC. Matching funds came from the Center for Pharmacoepidemiology, which is based in the epidemiology department of the Gillings School of Global Public Health and Diabetes Care Center in the UNC School of Medicine.

The article, "Dipeptidyl-peptidase-4 inhibitors and pancreatic cancer: a cohort study," was published online August 11 and is in the September print issue of Diabetes, Obesity and Metabolism. Gokhale is the lead author. Other authors include Buse, Christine Gray, MPH, Til Sturmer, MD, PhD, Virginia Pate, MS, and M. Alison Marquis, MStat, all from the UNC Gillings School of Global Public Health.