Gastroenterology: Metformin can reduce risk of pancreatic cancer

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Taking the most commonly-prescribed anti-diabetic drug, metformin, reduces an individual's risk of developing pancreatic cancer by 62 percent, according to research from the University of Texas M. D. Anderson Cancer Center, published in the Aug. 1 issue of Gastroenterology.

"This is the first epidemiological study of metformin in the cancer population, and it offers an exciting direction for future chemoprevention research for a disease greatly in need of both treatment and prevention strategies," said Donghui Li, PhD, a professor in M. D. Anderson's department of gastrointestinal medical oncology.

According to Li, more than 35 million prescriptions for the drug are filled annually, and it is most often given to type 2 diabetic patients who are obese or have insulin resistance.

"Metformin works by increasing the cellular sensitivity to insulin and decreasing its level circulating in diabetics. Insulin also seems to have a growth-promoting effect in cancer," said Li, the study's senior author. "Metformin activates the AMP kinase, which is a cellular engery sensor. Recent publications have described that AMP kinase also plays an important role in the development of cancer by controlling cell division and growth.

"Given these earlier findings, and knowing that diabetes is a risk factor for the development of pancreatic cancer and that 10 percent of such cancers are associated with diabetes, we wanted to better understand the specific association between different anti-diabetic therapies and this lethal disease," she explained.

For the case control study, the researchers enrolled 1,838 participants--973 patients with pancreatic adenocarcinoma treated at M. D. Anderson between 2004 and 2008--to compare 863 cancer-free individuals, all companions of M. D. Anderson patients. Of all participants, 259 patients and 109 controls were diabetics. The groups were matched by age, race and sex. Personal interviews were conducted to collect such information as their smoking history, family history of cancer, alcohol use and body mass index throughout their lives. Diabetics were also asked about their anti-diabetic medication history.

Researchers categorized diabetics by their use of four common classes of anti-diabetic therapies --insulin or insulin secretagogues, metformin, thaizolidinediones (TZDs), or other common anti-diabetic therapies and the duration of use.

The investigators found that diabetics who took metformin alone, or in any combination with other diabetic therapies, had a 62 percent reduction of risk for developing pancreatic cancer, compared with those who never used the drug. When the analysis was restricted to those who never used insulin or those who had diabetes more than two years, the protective effect of metformin remained significant. Other diabetes-associated risk factors, such as a history of smoking, overweight or obesity and glycemic control, did not have a significant effect on the relationship between metformin use and pancreatic cancer risk.

Conversely, diabetics who had taken insulin or insulin secretagogues had a 4.99- and 2.52-fold increased risk for the disease, respectively, compared with never users.

Findings regarding TZDs and the other drug classes and the risk of pancreatic cancer were inconclusive because of the small sample size; a larger cohort is needed to understand the association between their use and pancreatic cancer, the authors noted.

Li said the study is not without limitations, including the relatively small size of the study's diabetic population; she hopes the research will be replicated in a larger sample size. Still, the findings present the immediate opportunity to explore metformin as a chemopreventive agent, according to the authors.

"While further validation is needed, our findings show metformin's potential as a chemopreventive agent," said Li. "Currently, once pancreatic cancer is diagnosed, we have few successful therapeutic agents to offer our patients, so obviously, for those at greatest risk, a preventive mechanism such as metformin would be a welcome option."

In a corresponding editorial, Yu-Xiao Yang, M,D, of the University of Pennsylvania School of Medicine in Philadelphia, noted that the American Diabetes Association, as well as the European Association for the Study of Diabetes, have both recommended the inclusion of metformin for all type 2 diabetes patients without contraindications. Yang noted that the possible chemopreventive properties of the