Metformin Use Is Associated with Better Survival of Diabetic Patients with Pancreatic Cancer

Abstract

Purpose Accumulating evidence suggests that metformin has antitumor activity. The aim of this study was to determine whether metformin use has a survival benefit in patients with pancreatic cancer. Experimental Design We conducted a retrospective study of diabetic patients with pancreatic cancer treated at MD Anderson Cancer Center. Information on diabetes history including treatment modalities and clinical outcome of pancreatic cancer was collected using personal interviews and medical record review. Survival analysis was carried out using a Kaplan Meier plot, log-rank test, and Cox proportional hazards regression models. Results Among the 302 patients identified, there were no significant differences in demographic or major clinical characteristics between the patients who had received metformin (n=117) and those who had not (n=185). The 2-year survival rate was 30.1% for the metformin group and 15.4% for the nonmetformin group (P=0.004, χ2 test). The median overall survival time was 15.2 months for the metformin group, and 11.1 months for the nonmetformin group (P=0.004, log-rank test). Metformin users had a 32% lower risk of death; the hazard ratio (95% confidence interval) was 0.68 (0.52–0.89) in a univariate model (P=0.004), 0.64 (0.48–0.86) after adjusting for other clinical predictors (P=0.003), and 0.62 (0.44–0.87) after excluding insulin users (P=0.006). Metformin use was significantly associated with longer survival in patients with non-metastatic disease only. Conclusions Our finding that metformin use was associated with improved outcome of diabetic patients with pancreatic cancer should be confirmed in independent studies. Future research should prospectively evaluate metformin as a supplemental therapy in this population.

Mechanism of Metformin-dependent Inhibition of Mammalian Target of Rapamycin (mTOR) and Ras Activity in Pancreatic Cancer

“…Recent studies report that diabetic cancer patients who take metformin exhibit improved outcomes as compared with patients taking other antidiabetic drugs (10), and this has spurred interest in possible clinical applications of metformin for cancer therapy. One of the hallmarks of metformin action is associated with inhibition of the mTOR signaling in both cancer and non-cancer tissues and cells (15)(16)(17)(18)(19)(20)(22)(23)(24)(25).…”

“…A comparable study in pancreatic cancer patients showed that diabetics using metformin had a 32% lower risk of death and longer overall survival than diabetics using other drugs (10). This latter study recommended using metformin as a supplemental therapy for treatment of pancreatic cancer patients (10).…”

“…In one study, the overall survival of type II diabetic patients with colorectal cancer was 76.9 months for individuals treated with metformin as compared with 56.9 months for those receiving other diabetic medications, and this represented a 30% improvement in overall survival (6). A comparable study in pancreatic cancer patients showed that diabetics using metformin had a 32% lower risk of death and longer overall survival than diabetics using other drugs (10). This latter study recommended using metformin as a supplemental therapy for treatment of pancreatic cancer patients (10).…”

“…It has been shown that cancer rates in diabetics using metformin are lower than in patients using other insulin-sensitizing agents (2,(5)(6)(7)(8)(9)(10)(11)(12). In one study, the overall survival of type II diabetic patients with colorectal cancer was 76.9 months for individuals treated with metformin as compared with 56.9 months for those receiving other diabetic medications, and this represented a 30% improvement in overall survival (6).…”

Carbon Source and Myc Expression Influence the Antiproliferative Actions of Metformin

“…Some pharmacoepidemiologic studies have suggested that metformin may have antineoplastic activity (21)(22)(23)(24)(25)(26)(27) but others have not supported this view (28)(29)(30)(31). Similarly, some (10) but not all (32) laboratory studies suggest that metformin has antineoplastic activity.…”