Metformin enhances the response to radiotherapy in diabetic patients with rectal cancer

Metformin may have anticancer effects and could improve response to radiotherapy in several malignancies. We aimed to investigate the effect of metformin on response to radiotherapy in rectal cancer. A total of 543 rectal cancer patients who were treated with neoadjuvant chemoradiotherapy followed by radical surgery from January 2007 to December 2011 were reviewed. Patients were divided into three groups: diabetics taking metformin (n = 42), diabetics not taking metformin (n = 29), and non-diabetics (n = 472). Tumor response and survival were compared between groups. The rates of N downstaging and tumor regression grades (TRG) 3-4 were significantly higher in diabetics taking metformin (p = 0.006 and p = 0.029, respectively). There were no significant differences between groups in terms of T downstaging and pathologic complete response. On multivariate analysis, metformin use was associated with increased rates of N downstaging and TRG 3-4 (p = 0.003 and p = 0.019, respectively). Recurrence-free survival, disease-free survival, and overall survival rates were not significantly different between groups. Metformin is associated with higher tumor response rates to radiotherapy in rectal cancer, especially in patients with diabetes.