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

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.

Dipeptidyl peptidase-4 inhibitors and cancer risk in patients with type 2 diabetes: a meta-analysis of randomized clinical trials

“…A few studies also investigated the association between DPP4i and other types of cancer. A retrospective cohort study assessed the risk of prostate cancer associated with sitagliptin, also using the Taiwanese database of the National Health Insurance between 1999 and 2000, and the result of HR = 0.613 (95% CI = 0.493–0.763) showed that sitagliptin could significantly reduce the risk of prostate cancer 49 . Some in vivo studies explored the effect of DPP4 on tumorigenesis of the breast, ovary and prostate at the molecular level; however, it was not conclusive whether DPP4 promoted tumorigenesis 50 – 52 .…”

Antiproliferative and Apoptogenic Efficacy of Antidiabetic Drugs Metformin and Sitagliptin Against McF7 and Hepg2 Cancer Cells: A Comparative Molecular Study

“…Metformin and Sitagliptin induced Capase3 activity dose dependently though sitagliptin did show a significantly lower effect than the other drugs. But to summarize the experiments, it should be emphasized that sitagliptin, unlike previous reports from various investigators 2,[18][19][20][21][22] , has been observed to show cell-death inducing characters.…”

Sitagliptin and oral cancer risk in type 2 diabetes patients

“…The PS was derived from all characteristics and the date of entry by logistic regression. This matching method has been used and described in detail in our previous studies [ 6 , 28 – 31 ].…”

“…Hazard ratios comparing different subgroups of sitagliptin exposure to never users were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the PS [ 38 ]. Because sitagliptin may increase or decrease the risk of some other cancers [ 1 – 6 ], sensitivity analyses were conducted after excluding patients who developed other cancers during follow-up. To examine whether sitagliptin might also increase or decrease the risk of oral diseases that may predispose to oral cancer, the incidence of “gingival and periodontal diseases” and/or “oral mucosal lesions” and hazard ratios were also calculated.…”

“…A Japanese case report showed that sitagliptin treatment for 3 weeks dramatically regressed hepatocellular carcinoma in a patient with hepatitis C infection [ 5 ]. In a recent observational study, sitagliptin reduced the risk of prostate cancer [ 6 ].…”