Prognostic significance of anti-diabetic medications in pancreatic cancer: A meta-analysis

The role of anti-diabetic medications in pancreatic cancer remains conflicting. We carried out a systematic search of Pubmed and Embase databases for studies published before August 2016, which assessed the associations between anti-diabetic medications (metformin, sulfonylureas, thiazolidinediones and insulin) intake and pancreatic cancer prognosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Fourteen studies enrolling 94778 participants were eligible for inclusion, with 12 cohort studies and 2 randomized controlled trials (RCTs). Significant association between metformin (adjusted HR=0.77, 95% CI=0.68-0.87) use and OS was found in cohort studies, whereas no significant association between metformin use and PFS (HR=1.22; 95% CI=0.76-1.95) or OS (HR=1.20, 95% CI=0.84-1.72) in RCTs. No significant survival benefits were identified for insulin (HR=1.18, 95% CI=0.83-1.69), sulfonylureas (HR=1.03, 95% CI=0.81-1.30), or thiazolidinediones (HR=0.84, 95% CI=0.58-1.22). The trim-and-fill method and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. Our findings provide strong evidence that metformin is associated with improved OS in pancreatic cancer patients in cohort studies. However, the effect of other anti-diabetic medications should be interpreted with caution owing to the limited number of studies.