Association of dipeptidyl peptidase 4 inhibitors with risk of metastases in patients with type 2 diabetes and breast, prostate or digestive system cancer.
OBJECTIVE
Experimental and animal studies have supported the hypothesis that dipeptidyl peptidase-4 inhibitors (DPP-4i) may accelerate tumor metastasis. The aim was to analyze the relationships between DPP-4i therapy with risk of metastases in type 2 diabetes patients with breast, prostate and digestive organ cancers.


METHODS
Type 2 diabetes patients with first diagnoses of breast, prostate or digestive organ cancer were selected in general and internal medicine practices (Disease Analyzer Germany: 01/2008-12/2014). Propensity score matching between DPP-4i users and non-users was carried out for age, sex, diabetes duration, and metformin use. Time-dependent Cox regression models were used to estimate hazard ratios (HR) for metastases further adjusting for HbA1c, body mass index, comorbidity and co-therapy with glucose-lowering drugs (3-4years follow-up).


RESULTS
668 patients with newly diagnosed breast cancer, 906 with prostate cancer and 908 with digestive organ cancer were analyzed. In Cox regression, use of DPP-4i was not associated with an increased risk of metastases in patients with breast (adjusted HR, 95%CI: 1.00, 0.49-2.02), prostate (0.98, 0.54-1.77) or digestive organ cancers (0.97, 0.57-1.66).


CONCLUSIONS
This first observational study in patients with type 2 diabetes and breast, prostate or digestive organ cancer found no increased risk of metastases in DPP-4i users.
Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
Wolfgang
W
Rathmann
Epidemiology, QuintilesIMS, Frankfurt, Germany. Electronic address: kkostev@de.imshealth.com.
Karel
K
Kostev
D000368:Aged; D001943:Breast Neoplasms / Q000150:complications*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004067:Digestive System Neoplasms / Q000150:complications*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D018572:Disease-Free Survival; D057286:Electronic Health Records; D005260:Female; D005858:Germany / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D009362:Neoplasm Metastasis; D015995:Prevalence; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000150:complications*; D012189:Retrospective Studies; D012306:Risk
D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
Breast cancer; Digestive system cancer; Dipeptidyl peptidase 4 inhibitors; Prostate cancer; Type 2 diabetes