Diabetes Drug's Dark Side

Januvia and Byetta for type 2 diabetes associated with increased risk of pancreatic cancer and pancreatitis

(RxWiki News) There have been huge strides in the fight against diabetes over the past decade. Patients now have more treatment and drug options than they ever did before. Yet, some of these drugs may not be entirely safe.

Two kinds of drugs for treating type 2 diabetes may be associated with a higher risk of pancreatic cancer and pancreatitis - a condition in which the pancreas becomes inflamed. One of the drugs may also increase the risk of thyroid cancer.

"Discuss potential diabetes drugs side effects with your pharmacist."

In past studies, researchers found that these two diabetes drugs had unintended effects on the pancreas of animals. These effects were cause for concern for Dr. Peter Butler, director of the Larry L. Hillblom Islet Research Center at the University of California, Los Angeles, and his colleagues.

According to Dr. Butler, if the drugs have the same effects in humans, then they are likely to increase the risk for pancreatic cancer and pancreatitis.

The two drugs being called into question are Januvia (sitagliptin) and Byetta (exenatide). Both drugs are used to treat type 2 diabetes. Each works in different yet related ways to lower blood sugar in diabetes patients.

"These two [drugs] work by increasing the levels of a hormone called incretin," explains Steven Kussin, M.D., FACP, a gastroenterology expert and found of central New York's only Shared Decision Center. "They have a direct effect on pancreatic cells. It’s how they work. Incretin drives pancreatic cells’ replication. In animal experiments, one week of Januvia or Byetta increased pancreatic weight and promoted genetic changes that might increase the chance of pancreatitis. Any chronic pancreatic inflammation may predispose patients to pancreatic cancer."

"Every treatment for diabetes type II has tradeoffs," Dr. Kussin also notes. "No single agent is risk free. Patients should be aware of the strengths and weaknesses of each medication.

With the results of the animal studies on their minds, Dr. Butler and his colleagues looked at the U.S. Food and Drug Administration's database for negative side effects reported by patients using Januvia and Byetta between 2004 and 2009.

They found that patients taking these drugs were six times more likely to develop pancreatitis, compared to patients going through four other types of treatment. The rate of pancreatic cancer was 2.9 times higher in patients taking Byetta and 2.7 times higher in those taking Januvia, compared to those on other treatments.

What's more, the researchers also found that patients taking Byetta had an increased risk of thyroid cancer. Patients taking Januvia did not experience this increased risk.

"It is however worth remembering that these agents are effective in reducing blood sugar," says Dr. Kussin. "They, unlike some other diabetes therapies, do not cause heart disease. It was recently shown that they may actually protect the heart. In addition these agents, unlike others, are also effective in decreasing the appetite and helping increase weight loss.

"Patients then might need to make a tradeoff between potential increases in pancreatic cancer, a fatal but uncommon cancer, that kills 36,000 people per year vs. taking an alternative drug that increases the chances of becoming a victim of our nation’s number one cause of death: heart disease that kills over 600,000 Americans each year."

Dr. Butler and colleagues acknowledge that the FDA's adverse events database has its limitations, such as incomplete data and reporting biases. However, says Dr. Butler, it also has the advantages of being large, easy to access, and independent from the drug companies.

He argues that the results from the animal studies and the evidence in the FDA database suggest that more research needs to be done to see if these new and widely available drugs are in fact increasing the risk of pancreatic cancer and pancreatitis.

The study's authors write that the best way to continue research on these drugs is through randomized, controlled clinical trials.

This observational study - which was funded by the Larry L. Hillblom Foundation - is published in the journal Gastroenterology.

Review Date: 
September 19, 2011