e21617 Background: Although hypoglycemic agents (metformin, insulin, sulfonylureas [SUs] and thiazolidinediones [TZDs]) may influent prognosis of cancer at several sites, very little is known about their effects on clinical outcomes of lung cancer patients with diabetes mellitus (DM) and results from clinical trials are often inconsistent. Methods: To assess the association between hypoglycemic agents and clinical outcomes of lung cancer, we performed a systematic review of published studies from PubMed, EMBASE, Web of Science and The Cochrane Library up to January, 2016. Meta-analysis was performed to calculate the pooled hazard ratio (HR) and 95% confidence interval (95% CI). Results: The pooled HRs favoring metformin users was 0.77 for overall survival (OS) (n = 12, 95% CI: 0.66-0.89) and 0.59 for disease-free survival (DFS) (n = 6, 95% CI: 0.47-0.72). Only one study assessed the relation between metformin and cancer-specific survival (CSS) in lung cancer patients, reporting no statistically significant results. No significant association between insulin use and OS (n = 2, HR: 0.95, 95% CI: 0.79-1.13) or CSS (n = 2, HR: 1.03, 95% CI: 0.76-1.41) was noted. Only one study evaluated the effect of SUs in patients with lung cancer and reported no statistically clinical benefit (HR: 1.10; 95% CI: 0.87-1.40). Likewise, one study evaluated the effect of TZDs on OS in patients of lung cancer and reported no significant difference between TZDs and non-TZDs groups (HR: 1.04, 95% CI: 0.65-1.66). Conclusions: This meta-analysis demonstrated that metformin could improve survival outcomes of patients with lung cancer and DM. No association between insulin, TZDs or SUs and lung cancer outcomes was found.