Effect of Metformin on Overall Survival of Upper Tract Urothelial Carcinoma in Patients with Type 2 Diabetes
Kuan-Hsien Wu2, Chien-Sheng Wang2, Ching-Chia Li2,3,4, Yung-Shun Juan1,2,3,4, Wen-Jeng Wu2,3,4, Hsiang-Ying Lee1,2,3,4*
1 Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
2 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
3 Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
4Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Purpose: Metformin, a widely used oral anti-diabetes drug, has been proposed in several studies that it may play a possible protective role in several cancer recurrence and mortality. And yet, the exact mechanism and efficacy of metformin on urothelial cancer, especially upper tract urothelial carcinoma (UTUC), remain to be investigated.
In this study, by conducting a population-based analysis, we aim to investigate if metformin can improve the survival rate in upper tract urothelial carcinoma patients.
Materials and Methods: In this retrospective population-based longitudinal cohort study in men 40 years or older with documentation of UTUC, data were collected from the registry of the Taiwan National Health Insurance (NHI) database for patients with UTUC and type 2 diabetes mellitus (T2DM). Patients who have taken at least two prescriptions of metformin were included in the study cohort as ever-users, and the other patients who have never used metformin were included in the control cohort (never-users). The hazard ratios was calculated by Cox regression for ever-users and never-users.
Results: Among the 781 enrolled patients, 439 patients were included as ever-users, and another 342 patients were included as never-users. The median survival time is 3.95 years in never-users cohort compared to 6.90 years in ever-users cohort, which remained statistically significant in both univariate and multivariable analysis (adjusted HR = 0.63 and 0.72, p= 0.0001 and 0.011, respectively). Furthermore, subgroup analysis showed that continuous usage of metformin from before to after the diagnosis of UTUC is associated with even better survival benefit. We also analyzed the patients who underwent radical nephroureterectomy, and it still indicated that metformin users had a better overall survival rate than non-users. The median survival time of metformin ever-user and non-user were 7.01 years and 5.27 years respectively in this operation subgroup, p = 0.004
Conclusions: This study suggests that metformin use improved any-cause mortality of patients with UTUC and T2DM.