Impact of DPP4 Inhibitors in Survival of Patients With Prostate, Pancreas, and Breast Cancer

Abstract

Background: Dipeptidyl peptidase-4 (DPP4), a cell surface protein, exhibits a crucial role in tumor biology and regulation of the immune system. We aim to study the impact of DPP4 inhibitors (DPP4i) in patients with prostate cancer (PRC), pancreatic cancer (PC) and breast cancer (BC). Methods: Using the SEER and Medicare linked database, we identified patients with PRC or PC or BC with coexisting type II diabetes mellitus between 2007 and 2015. Patients were classified into four groups: (1) not on either DPP4i or metformin (reference group), this group included patient that were on anti-diabetic agents other than metformin or DPP4i (2) metformin only, (3) DPP4i only, and (4) DPP4i along with metformin (combination group). Overall survival (OS) analyses were performed using SAS ® , version 9.4. Results: We identified 15,330 patients with PRC, 5,359 patients with PC and 16,085 patients with BC. In PRC cohort, patients on DPP4i had significant survival advantage with HR 0.77 (95% CI: 0.64-0.93), P = 0.005 when compared to the reference group. Patients taking metformin also had significant OS benefit with HR 0.87 (95% CI: 0.81-0.93), P < 0.0001 when compared to the reference group. However, in BC cohort, OS did not favor the patients taking DPP4i with HR 1.07 (95% CI: 0.93-1.25, P = 0.33). Similarly, in PC cohort, OS was indifferent for the patients on DPP4i with HR 1.07 (95% CI: 0.93-1.24, P = 0.68). Upon subgroup analyses of PRC patients, the survival favored the group taking DPP4i, irrespective of stage, use of chemotherapy, androgen-deprivation therapy, and prostatectomy or radiation therapy. Conclusions: DPP4i seems to improve survival in PRC patients; however, not in PC or BC patients. While the exact mechanism involved remains to be elucidated, a prospective clinical trial would help to confirm these findings.

Immune Interaction Map of Human SARS-CoV-2 Target Genes: Implications for Therapeutic Avenues

“…The inhibition of DPP4 led to the suppression of breast cancer tumor growth ( 51 ) and displayed a positive trend in OS of colorectal cancer ( 52 ) and prostate cancer ( 53 ). Analysis of colorectal cancer and lung cancer patients showed a similar trend toward beneficial effects associated with DPP4 inhibition ( 54 ); however, further studies are required on the clinical impact of DPP4 inhibition on tumor patients.…”

The Influence of Anti-Diabetic Drugs on Prostate Cancer

“…Early cell lines and animal studies on prostate cancer showed that increased expression of DPP-4 may play an important role as a factor suppressing the long-period progression of the disease [ 91 ]. But, recent results of clinical trials showed the opposite [ 92 , 93 ]. Such contrary results may be due to the activity of DPP-4 on many substrates, which were not present, nor taken into consideration during cell line studies.…”

“…Recent retrospective cohort analysis of 15,330 patients with PC and diabetes showed that use of DPP-4 inhibitors only ( n = 441) (HR 0.77; 95% CI: 0.64–0.93) and in combination with metformin ( n = 820) (HR 0.80; 95% CI: 0.68–0.94) had a significant overall survival (OS) benefit compared to the reference group (not on either DPP4 inhibitors or metformin). In addition, DPP-4 inhibitors show a trend to bring neutral or favorable results in subgroup analyses of PC patients irrespective of the stage (stage I not reliable; stage II HR 0.70, 95% CI: 0.54–0.9; stage III HR 0.96, 95% CI: 0.26–3.55; stage IV HR 0,81 95% CI: 0.53–1.26), treatments with chemotherapy (HR 0.84, 95% CI: 0.65–1.08 with chemotherapy and HR 0.71, 95% CI: 0.53–0.95) without chemotherapy), androgen-deprivation therapy (ADT) (HR 0.87, 95% CI: 0.69–1.15 with ADT and HR 0.67, 95% CI: 0.5–0.84 without ADT), prostatectomy (HR 0.27, 95% CI: 0.04–2.00 with prostatectomy and HR 0.78, 95% CI: 0.65–0.95 with no prostatectomy), or radiation (HR 0.84, 95% CI: 0.59–1.19 with radiation therapy and HR 0.73, 95% CI: 0.58–0.91 without radiation therapy), however because of low sample size some of this data was not statistically significant [ 93 ].…”

A Multi-Center Retrospective Analysis Examining the Effect of Dipeptidyl Peptidase-4 Inhibitors on Progression-Free Survival in Patients With Prostate Cancer

“…Shah et al recently established that DPP4 inhibitors offer a significant survival advantage in prostate cancer [5]. Malignant prostate tissue was found to contain higher levels of DPP4/CD26 compared to benign tissue.…”