Sitagliptin may reduce prostate cancer risk in male patients with type 2 diabetes

Chin-Hsiao Tseng

doi:10.18632/oncotarget.12137

Abstract

This retrospective cohort study evaluated the risk of prostate cancer associated with sitagliptin use in Taiwanese male patients with type 2 diabetes mellitus by using the reimbursement databases of the National Health Insurance. Male patients with newly diagnosed type 2 diabetes mellitus at an age ≥25 years between 1999 and 2010 were recruited. A total of 37,924 ever users of sitagliptin and 426,276 never users were followed until December 31, 2011. The treatment effect of sitagliptin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Analyses were also conducted in a 1:1 matched pair cohort based on 8 digits of propensity score. Results showed that during follow-up, 84 ever users and 2,549 never users were diagnosed of prostate cancer, representing an incidence of 140.74 and 240.17 per 100,000 person-years, respectively. The hazard ratio (95% confidence intervals) for ever users versus never users was 0.613 (0.493-0.763). The respective hazard ratio for the first, second, and third tertile of cumulative duration of sitagliptin use <5.9, 5.9-12.7 and >12.7 months was 0.853 (0.601-1.210), 0.840 (0.598-1.179) and 0.304 (0.191-0.483), respectively; and was 0.856 (0.603-1.214), 0.695 (0.475-1.016) and 0.410 (0.277-0.608) for cumulative dose <15,000, 15,000-33,600 and >33,600 mg, respectively. Findings were supported by analyses in the matched cohort. In conclusion, sitagliptin significantly reduces the risk of prostate cancer, especially when the cumulative duration is >12.7 months or the cumulative dose >33,600 mg.

Highlights

The incidence of prostate cancer varies among different countries by 25-fold with higher incidence in developed countries in Europe and North America and lower incidence in less developed countries in Asia and Africa [1]
Patients with type 2 diabetes mellitus (T2DM) suffer from a higher risk of cancer, which can be related to obesity, insulin resistance, hyperinsulinemia, glycemic control, comorbidities or antidiabetic drugs [4,5,6,7,8,9,10,11]
Metformin significantly reduces prostate cancer risk [16], www.impactjournals.com/oncotarget but insulin was neither predictive for its incidence [17] nor for its mortality [18]

Summary

Introduction

The incidence of prostate cancer varies among different countries by 25-fold with higher incidence in developed countries in Europe and North America and lower incidence in less developed countries in Asia and Africa [1]. While the temporal trends of prostate cancer incidence are decreasing in developed countries, they are increasing remarkably in the Asian populations [1]. In Taiwan, the age-standardized incidence of [2] and mortality from [3] prostate cancer are both increasing. Studies conducted in Taiwan suggested a significantly higher risk of prostate cancer in patients with T2DM in terms of incidence [2], prevalence [14] and mortality [3]. A recent meta-analysis conducted in the Asian populations strongly supported a higher risk of prostate cancer in patients with T2DM [15]. Metformin significantly reduces prostate cancer risk [16], www.impactjournals.com/oncotarget but insulin was neither predictive for its incidence [17] nor for its mortality [18]

Methods

Results

Conclusion