Diabetes drugs tied to pancreatic cancer risk

SUMMARY: Women taking the diabetes drug metformin had fewer cases of pancreatic cancer. Other diabetes drugs were linked with a higher risk. Men on metformin did not have the same lowered risk as women.

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NEW YORK (Reuters Health) - A new study links the diabetes drug metformin to fewer cases of pancreatic cancer -- at least in women -- but finds other diabetes medications are associated with a higher risk of the disease.

The differences in medication history among people who did or didn't get pancreatic cancer were small, researchers said, and it's unclear why the drugs might affect cancer risks in men and women differently.

Still, the new finding is in line with previous research suggesting that metformin may decrease the risk of multiple cancers, said Dr. Peter Butler, a diabetes researcher at the University of California, Los Angeles David Geffen School of Medicine, who wasn't involved in the new study.

"One theme that seems to be coming through... is that the oldest drug we have for diabetes, metformin, is undoubtedly the best drug we have for diabetes," he told Reuters Health.

Pancreatic cancer is relatively rare as far as cancers go, but progresses quickly; most people don't survive more than a couple years after diagnosis. The National Cancer Institute estimates that about 44,000 people will be diagnosed with pancreatic cancer in the United States this year, and close to 38,000 will die from the disease.

Research has suggested that people with pancreatic cancer may have an increased risk of diabetes, but it's unclear how diabetes -- and the drugs used to treat it -- may affect pancreatic cancer risks in previously cancer-free people.

To help answer that question, Dr. Christoph Meier of the University Hospital Basel in Switzerland and his colleagues consulted a database of more than eight million people in the UK, including about 2,800 who were diagnosed with pancreatic cancer between 1995 and 2009.

For each of those people, they found another six of the same age and gender that didn't have pancreatic cancer to serve as a comparison group.

Using records from primary care doctors, the researchers determined how many people in the pancreatic cancer and cancer-free groups had previously been diagnosed with diabetes and were on an anti-diabetes drug, such as metformin or sulfonylureas, which include glimepiride and glyburide.

Those drugs cause the body to make or absorb less glucose (metformin) or to produce more insulin (sulfonylureas) to keep blood sugar levels in check.

One in nine people with pancreatic cancer had a prior diagnosis of diabetes, compared to about one in twelve in the cancer-free comparison group, according to findings published Tuesday in the American Journal of Gastroenterology.

According to their medical records, two percent of people with pancreatic cancer had been taking metformin long-term before they were diagnosed, compared to 1.6 percent of the group without cancer -- a difference that could have been due to chance.

But when the researchers separated the records by gender, they found that significantly fewer women with a new diagnosis of pancreatic cancer had been taking metformin for at least a few years, compared to cancer-free women.

That was after the researchers had already taken into account whether women were overweight or obese and if they smoked or drank alcohol.

The association in one gender but not the other was "somewhat unexpected," according to Meier's team, and there's no clear biology-based way to explain why metformin might help protect women against pancreatic cancer, but not men.

The findings were reversed for insulin and sulfonylureas in the study population. Significantly more people with pancreatic cancer had a history of long-term use of those drugs than cancer-free people.

Craig Currie, who has studied diabetes drugs and cancer at the Cardiff University School of Medicine in the UK, said it makes sense that insulin and sulfonylureas would increase the risk of pancreatic cancer. Insulin promotes cancer growth, he said, and also acts directly on the pancreas.

The study's investigators "raise doubts about these treatments," he told Reuters Health in an email.

"There is a possibility that exogenous insulin (insulin that's not made naturally by the body) is of questionable safety in people with type 2 diabetes," added Currie, who didn't participate in the new research.

Still, absolute differences in medication use were small even in people with cancer: less than one percent of those with or without pancreatic cancer had taken insulin long-term. Sulfonylurea users accounted for just over three percent of people with a new pancreatic cancer diagnosis and two percent without cancer.

Butler said it's hard to tease out what cancer risks may be due to the drugs, and what could be a result of poor diet and lack of exercise, for example, in people with diabetes. He said that more research will be needed to tease out those specific effects.

"Honestly for patients at this point, I think this is another piece of the jigsaw puzzle," Butler said.

"This paper in itself would not cause me to recommend a change in treatment for people."

That said, Butler concluded that evidence suggests most people with type 2 diabetes who don't have any medical reasons not to take metformin should be on the drug, either alone or in combination with other anti-diabetes medications.

SOURCE: http://bit.ly/kkA6Tc American Journal of Gastroenterology, online January 31, 2012.