Relationships are between metformin use and survival in pancreatic cancer patients concurrent with diabetes: A systematic review and meta-analysis

BACKGROUND: Increased risk and cancer-related mortality is observed in pancreatic cancer (PC) patients with diabetes mellitus (DM). Whether using metformin as glucose-lowering therapy can result in survival benefit in this group of patients is still unclear. METHODS: A meta-analysis of 21 studies that including 38,772 patients was performed to investigate the association between metformin and overall survival in patients with PC and concurrent DM. RESULTS: A significant survival benefit was observed in metformin treatment group compared with non-metformin group (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.74–0.91). These associations were observed in both subgroups of Asian countries (HR = 0.69, 95% CI: 0.60–0.79) and Western countries (HR = 0.86, 95% CI: 0.76–0.95), the former was more obvious. Survival benefit was gained for patients at early stage (HR = 0.75, 95% CI: 0.64–0.85) and mixed stage (HR = 0.81, 95% CI: 0.70–0.91), but not for patients at advanced stage (HR = 0.99, 95% CI: 0.74–1.24). Similarly, survival benefit was also observed in patients receiving surgery (HR = 0.82, 95% CI: 0.69–0.94) and comprehensive treatment (HR = 0.85, 95% CI: 0.77–0.93), but not in chemotherapy group (HR = 0.99, 95% CI: 0.67–1.30). No obvious benefit was suggested when pooled by time-varying COX model (HR = 0.94, 95% CI: 0.86–1.03). CONCLUSIONS: These results suggest that metformin is associated with survival benefit in patients with PC and concurrent DM. Further randomized controlled trials and prospective studies with larger sample sizes are required to confirm our findings.