Dipeptidyl peptidase-4 inhibitors and mortality risks in patients with prostate cancer receiving androgen deprivation therapy: a population-based cohort study

Abstract

Background Dipeptidyl peptidase-4 inhibitors (DPP-4I) have demonstrated survival benefit in patients with cancer, but their impact on patients with prostate cancer (PCa), especially with androgen deprivation therapy (ADT), is unclear. This study examined the impact of DPP-4I use on mortality risks in patients with type 2 diabetes (T2D) and PCa receiving ADT. Methods Adults with T2D and PCa who received metformin and ADT attending public hospitals in Hong Kong between 1 January 2006 and 31 March 2021 were retrospectively identified. Patients with < 6 months of chemical castration without bilateral orchidectomy, < 6 months of concurrent DPP-4I and ADT use, or missing baseline HbA1c were excluded. DPP-4I users had ≥ 6 months of concurrent DPP-4I and ADT use, while non-users never had DPP-4I use. Included patients were followed-up until 30 September 2021. The endpoints were PCa-specific mortality and all-cause mortality. Inverse probability treatment weighting was used to balance covariates. Results In total, 1465 patients (286 DPP-4I users and 1179 non-users; mean age 76.0 ± 7.9 years old) were analyzed. Over a mean follow-up of 4.0 ± 3.0 years, DPP-4I users had lower risks of PCa-specific mortality (weighted hazard ratio (wHR) 0.40 [95% confidence interval (CI) 0.26–0.59], p < 0.001) and all-cause mortality (wHR 0.59 [95% CI 0.48–0.73], p < 0.001). Such associations were independent of diabetic control. Moreover, the association between DPP-4I use and risks of PCa-specific mortality was independent of chemotherapy or androgen receptor signaling inhibitor use. Conclusions DPP-4I use is associated with decreased mortality risks in patients with T2D and PCa receiving ADT.