Metformin reduces pancreatic cancer risk

Diabetics who took metformin alone or in combination with other antidiabetic medications had a 62 percent lower risk of having pancreatic cancer (P=0.001) compared to diabetics who never used the drug, according to new research.

“Our study is the first to investigate different types of antidiabetic oral medications in pancreatic cancer patients and the first to show that metformin reduced the risk of pancreatic cancer. This finding suggests that the use of metformin among diabetics could prevent or delay the development of pancreatic cancer,” said lead study author Professor Donghui Li.

Li explained that long-term type 2 diabetes is a known risk factor for pancreatic cancer, with 10 percent of such cancers associated with diabetes. Li, who is a professor of medicine and epidemiology at the department of gastrointestinal medical oncology at the University of Texas M.D. Anderson Cancer Center at Houston, Texas, US, and her colleagues embarked on this study to understand the specific link between various antidiabetic therapies and pancreatic cancer.

In an accompanying editorial, Dr. Yu-Xiao Yang from the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, US, noted that both the American Diabetes Association and the European Association for the Study of Diabetes have recommended that metformin be included in the treatment of all type 2 diabetes patients without contraindications.

“A possible chemopreventive effect of metformin on pancreatic cancer may provide an additional incentive for patients and physicians to follow this recommendation,” he stated. [Gastroenterology 2009 Aug;137(2):412-5]

Interestingly, the study found that diabetics who used insulin had a fivefold increased risk of pancreatic cancer compared to those who never used the therapy (P<0.001) and diabetics on insulin secretion stimulators had a 2.5-fold increased risk of pancreatic cancer compared to those who never took them (P=0.005).

However, Li and colleagues stated in their paper that the association of insulin use and increased pancreatic cancer risk was confounded by diabetes duration and glycemic control. Many pancreatic cancer patients started insulin 2 years or less before being diagnosed with cancer. This could have been due to worsening diabetes caused by pancreatic cancer, the authors reported.

As such, the authors explained, the relationship between short-term use of insulin and pancreatic cancer “suggests reverse causality,” which means that pancreatic cancer that was not clinically apparent could have exacerbated diabetes in the 2 years preceding discovery of the cancer, leading patients to take insulin for glycemic control.

Nonetheless, they noted that a weak but significant association between long-term insulin use (more than 5 years) and greater risk of pancreatic cancer was observed (P=0.049).

“The association of insulin use and risk of pancreatic cancer is perhaps more accurately assessed among long-term users of insulin,” said Li, noting that this has to be further investigated in a larger study.

Li and colleagues did not observe any significant association between use of thiazolidinediones and pancreatic cancer risk.

The case control study involved 1,838 participants. Nine hundred and seventy-three patients had pancreatic ductal adenocarcinoma and 863 (controls) were cancer-free. There were 259 diabetics in the cancer group and 109 diabetics in the control group.

The groups were matched according to age, race and sex and were asked questions about their family history of cancer, smoking and alcohol consumption and body mass index.

Diabetics were asked questions about the time of diabetes diagnosis, kind of treatment they were on, and the length of therapy. They were then grouped by their use of well-known antidiabetic agents such as insulin, insulin secretagogues, metformin and thiazolidinediones and/or other common antidiabetic medicines, and the duration of use. Researchers then compared the frequencies of each type of therapy used between cancer patients and non-cancer controls. [Gastroenterology 2009 Aug;137(2):482-8]