Increased Cancer Risk
People with type 2 diabetes taking the drugs Januvia or Byetta might have an increased risk of developing pancreatitis and pancreatic cancer, a preliminary study suggests.
The study also found that Byetta (exenatide) may raise the risk of thyroid cancer.
Although the links aren't conclusive, they merit further investigation, the researchers noted.
"We have raised concern that there may be a link, but we haven't confirmed it," said lead researcher Dr. Peter Butler, director of the Larry L. Hillblom Islet Research Center
We need to do more work to figure out whether this is real or not."
Both drugs help control blood sugar levels by encouraging production of a hormone called glucagon-like peptide 1 (GLP-1).
Januvia (sitagliptin) and Byetta, an injectable drug, are a new way of treating type 2 diabetes, and they potentially have advantages over older medications, Butler said. But, because these drugs are new, they're "the ones we know least about," he said. "When new drugs come out, the long-term side effects of these drugs are not well understood."
For the study, recently published in the journal Gastroenterology, Butler's team used 2004-2009 information in the U.S. Food and Drug Administration's database on adverse events, which are reported by doctors whose patients use these drugs.
When compared to other treatments, the researchers found a sixfold increase of reported cases of pancreatitis (inflammation of the pancreas) linked to patients taking Januvia or Byetta; a 2.9-fold increase in reported cases of pancreatic cancer among those taking Byetta and a 2.7-fold increase of reported pancreatic cancers among Januvia users.
In addition, they also noted an increase in reported cases of thyroid cancer with Byetta.
This latest study builds on earlier research, published in a 2009 issue of Diabetes, which found an increase in pancreatitis in rats whose GLP-1 levels were raised, the researchers said.
Butler is quick to point out that these increases in pancreatic cancer risk, while statistically significant, are not specifically related to patients, but rather to an increase in doctors reporting these cases to the FDA.
"It is important to avoid alarmism and have people stop medicines that they may be benefitting from when the risk is not yet defined," he stressed.
"If the drug and you are working well together, I wouldn't say there is any reason to stop the drug, based on the evidence we have right now," he said. "But if you have any concern you should talk to your doctor about it."
Being overweight is an important risk for both pancreatic cancer and type 2 diabetes, Butler noted. So the first advice to overweight patients with type 2 diabetes is to lose weight. "By doing that, you reduce the risk of pancreatic cancer," he said.
In addition, the first medication used to control blood sugar in type 2 diabetics is metformin, which by itself may reduce the risk for pancreatic cancer, Butler said. Metformin is an older drug with a well-known safety profile, he noted.
Dr. Mary Ann Banerji, director of the Diabetes Treatment Center at SUNY Health Science Center Brooklyn in New York City, said that "this is not perfect data."
However, Banerji does not prescribe these drugs for patients who have had a history of pancreatitis or a family history of thyroid cancer. There are alternatives such as metformin and insulin, as well as Avandia and Actos, she said, but studies have turned up an increased risk for heart attack and heart failure in the last two drugs. The FDA has removed Avandia from pharmacy shelves, and the agency issued a warning last summer that there is a possible increased risk of bladder cancer in patients who take Actos for more than a year.
The concerns about Januvia and Byetta "should not be blown out of proportion," Banerji said. "You prescribe them on an individual basis, because, in the end, all of medicine is individual," she said. "We should use these drugs judiciously along with metformin."
Industry representatives, insisting that no studies involving these drugs have found an increased risk of pancreatitis or pancreatic cancer, stand by their products. The database used for the study contains information on doctor-reported cases and does not reflect cause-and-effect, they said.
Dr. Barry Goldstein, vice president and therapeutic area head for diabetes and endocrinology a Merek, which makes Januvia, said that "there has been no association shown between Januvia and pancreatitis."
"We have full confidence in Januvia, which is used by millions of patients around the world," he said.
Anne Erickson, a spokeswoman for the makers of Byetta, said that "the conclusions of the study are in contrast to other nonclinical, clinical and adequately conducted post-marketing epidemiological studies."
Epidemiological studies have not established a significantly increased risk of pancreatitis associated with Byetta, she said. "To date, the available data do not demonstrate that exenatide increases the overall risk of cancer in humans."
Another expert, Dr. Ronald Goldberg, professor of medicine, biochemistry and molecular biology at the University of Miami Miller School of Medicine, said the findings merit consideration. "I don't think the study is definitive, but it raises a flag and is clearly something we need to pay attention to going forward."
There is "more benefit than risk with these drugs, based on our current knowledge," he said.