Effects of metformin on survival outcomes of pancreatic cancer patients with diabetes: A meta-analysis

Pancreatic cancer risk is reduced by metformin treatment in patients with diabetes. However, the effect of metformin on pancreatic cancer overall survival is unclear. The aim of the present study was to determine the association between metformin and clinical outcomes of pancreatic cancer patients with diabetes. An electronic and manual search was conducted using PubMed, Web of Science, Medline-Ovid and Cochrane Library databases between the beginning and March 31, 2017. A total of 8 studies consisting of 4,293 patients with pancreatic cancer with diabetes were included, comprising 2,033 patients who had received metformin and 2,260 patients who had not. The meta-analysis showed that metformin was associated with a relative survival benefit in pancreatic cancer patients [hazard ratio (HR), 0.81; 95% confidence interval (CI), 0.70-0.93]. These associations were also observed in subgroups of Asian countries 0.64 (95% CI, 0.52-0.80) and Western countries 0.88 (95% CI, 0.82-0.95), as well as diabetes (no indication of diabetes type). Excluding the studies considered as be prone to immortal time bias resulted in HRs (95% CIs) of 0.86 (0.69-1.07). The results of this study support the notion that the use of metformin may improve the overall survival of patients with pancreatic cancer with concurrent diabetes. However, the proposed beneficial effect of metformin on pancreatic cancer survival may be based on immortal time bias. Further carefully designed studies with high quality are warranted to confirm this efficacy.