In the Clinic: Metformin and Pancreatic Cancer
Metformin, traditionally used as a first-line treatment for type 2 diabetes, may be able to reduce a potential source of energy for certain cancer cells.
By reducing blood glucose and improving insulin sensitivity, metformin, an oral medication that has traditionally been used as a first-line treatment for patients with type 2 diabetes, may be able to reduce a potential source of energy for certain cancer cells that express insulin receptors and require oxidative phosphorylation to replicate. Pancreatic cancer represents one such cancer that may significantly use oxidative phosphorylation, which has been observed in laboratory models.1
Metformin is a member of the biguanide family of medications that work through several molecular pathways including AMP-activated protein kinase, respiratory chain complex, and oxidative phosphorylation. With respect to diabetes, metformin uses its pathways to reduce glucose production from the liver and absorption in the small bowel along with increasing insulin sensitivity.
Mixed results with respect to the use of metformin in pancreatic cancer have been reported in retrospective epidemiological studies. Sadeghi and colleagues retrospectively evaluated approximately 300 patients with both diabetes and pancreatic cancer.2
Patients who received metformin had longer 2-year survival rates (30.1% vs 15.4%; P = .004) and lower risk of death (HR, 0.68; 95% CI, 0.52 - 0.89; P = .004) compared to those who did not receive metformin. However, these results were significant only in patients without metastatic disease.
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Similarly, Wang and colleagues performed a meta-analysis of 11 studies that showed a reduced risk of pancreatic cancer in diabetic patients receiving metformin (relative risk 0.63, 95% CI, 0.46 - 86; P = .003).3
Additional studies, such as Tsilidis and colleagues have not shown as much promise.4 After performing a retrospective cohort study of more than 95 000 patients, there was no benefit in receiving metformin with respect to preventing cancer.