For the first time, a case-control study has linked metformin use to a significant decrease in the risk of pancreatic cancer in patients with diabetes.
The study also found a suggestion that insulin and insulin secretagogues may be associated with an increased risk of pancreatic cancer, although this could have been a chance finding, reported Donghui Li, Ph.D., and her colleagues.
There is a plausible explanation for metformin's possible protective effect, wrote Dr. Li of the University of Texas M.D. Anderson Cancer Center, Houston, and her coauthors. The drug tends to reduce body weight, and obesity is a known risk factor for pancreatic cancer. Metformin also controls hyperglycemia and hyperinsulinemia—factors that mediate the adverse impact of diabetes on cancer. In vitro and in vivo experiments have shown that metformin is both an antioxidant and tumor growth inhibitor and that it protects against pancreatic tumors induced by chemicals and a high-fat diet.
Dr. Li's analysis used data extracted from an ongoing, hospital-based case-control study that began in 2004, designed to explore risk factors associated with pancreatic cancer. The Li analysis included 973 cases and 863 age- and sex-matched controls. Diabetes was present in 27% of the cases and 13% of the controls; it was associated with a 2.4-fold increased risk of pancreatic cancer (Gastroenterology 2009;137:482-8).
Compared with nondiabetic patients, however, those patients with diabetes who were taking metformin had a significant 62% decreased risk of pancreatic cancer. Patients with diabetes who took insulin had a 78% increased risk of pancreatic cancer, compared with nondiabetic patients, although this was not a significant difference.
The investigators then compared only patients with diabetes. Ever-users of metformin were 62% less likely to develop cancer than were never-users. Metformin's protective effect was somewhat diminished by two other strong risk factors: smoking and obesity. Among smokers, the use of metformin conferred a nonsignificant risk reduction of 56%, compared with nonsmokers who used the drug. “Similarly, the protective effect was significant in individuals of normal body weight (odds ratio 0.35) but not in those with excess body weight (body mass index of 25 kg/m2 or higher).”
Also among the patients with diabetes, ever-users of insulin were 5 times more likely to develop cancer than never-users, and ever-users of insulin secretagogues were 2.5 times more likely to develop the disease as well. Although the associations of increased risk and insulin were significant in that analysis, the authors wrote that they should be interpreted with caution. “Because of the small number of insulin secretagogue ever-users among controls, this observation could be by chance alone.”
Additionally, they noted, the risk of pancreatic cancer was increased for short-term users but not for long-term users, which does not support a biologic connection between the drug and the cancer.
Neither Dr. Li nor any of her coauthors reported a potential conflict of interest.
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