Metformin is associated with better survival rate of localized upper tract urothelial carcinoma patients with type 2 diabetes

Purpose: Metformin, an antidiabetic drug, has been proposed to play a possible protective role in cancer recurrence and patient mortality. However, the exact mechanism and efficacy of metformin in urothelial cancer, especially upper tract urothelial carcinoma (UTUC), remain unknown. In this study, we conducted a population-based analysis to investigate whether metformin could improve the survival rate of patients with UTUC. Materials and Methods: Males ≥40 years diagnosed with UTUC were included in this retrospective population-based longitudinal cohort study. Data were collected from the registry of the Taiwan National Health Insurance database for patients with UTUC and type 2 diabetes mellitus (T2DM). Patients who had received at least two prescriptions of metformin were included in the study cohort as ever-users, and patients who had never used metformin were included in the control cohort as never-users. The hazard ratios (HRs) were calculated using Cox regression for ever-users and never-users. Results: Among the 781 enrolled patients, 439 and 342 patients were included as ever-users and never-users, respectively. The median survival time was 3.95 years in the never-user cohort compared to 6.90 years in the ever-user cohort, which remained statistically significant in both univariate and multivariate analyses (HR = 0.63 and 0.72, P = 0.0001 and 0.011, respectively). Furthermore, subgroup analysis showed that continuous usage of metformin before and after the diagnosis of UTUC was associated with a better survival in patients with UTUC (adjusted HR = 0.72, 95% confidence interval: 0.55–0.93). Conclusion: This study shows a relationship between metformin usage and better survival outcome in patients with localized UTUC. The result may contribute a favorable anticancer role of metformin in localized UTUC and suggests that continuous metformin usage improves all-cause mortality in patients with localized UTUC and T2DM.