Mo1424 Effect of Anti-Diabetic Medications on the Presentation of Pancreatic Adenocarcinoma in Diabetic Patients

Background: Reports on the presence of insulin-like growth factor receptor pathways in pancreatic intraepithelial neoplasia (PanIN) lesions in mouse models and human pancreatic adenocarcinomas (PC) along with present controversy regarding the use of glucagon-like peptide-1 (GLP-1) agonists, highlights new concerns that diabetic (DM) treatments that increase insulin levels may accelerate the development of PC. To determine if this concern is of clinical significance, we hypothesized that those DM PC patients who were exposed to increased systemic insulin levels through the use of exogenous insulin or insulin-stimulating medications should have an earlier age of PC diagnosis or present at a more advanced stage than non-DM PC patients or insulin-independent treated DM PC patients. Methods: DM histories from patients enrolled in our PC Registry were reviewed. DM treatment history was obtained by a self-reported questionnaire filled out at time of registry enrollment. Electronic medical records were reviewed for confirmation and clarification of DM duration and anti-DM treatment regimens. Patients were stratified according to whether they were treated with insulin only, insulin-stimulating medications (eg. oral sulfonylureas, incretin mimetics, or meglitinides) only, or managed by insulin-independent strategies (eg. dietcontrolled, biguanides, or thiazolidinediones); those exposed to multiple classes of anti-DM medications were excluded from analysis. Eligible patients were analyzed by years between DM and age of PC diagnoses and PC stage using one-way ANOVA and chi-square test of association, respectively. Smoking and alcohol use were controlled during analysis with multivariable regression models. Results: Among 531 eligible PC patients (mean age: 66.3 ± 10.4 years): 132 DM (mean age:67.4 ± 10.3 years) were identified. The mean ages of PC diagnosis for patients within the insulin-only (n=46), insulin-stimulating (n=13), insulinindependent (n=73) and non-DM (n=318) cohorts were 69.0 ± 11.0 years, 68.8 ± 12.3 years, 66.2 ± 9.5 years, and 65.5 ± 10.5 years, respectively. As shown in Table, no significant difference among the age of PC diagnosis was seen based on duration or type of anti-DM treatment. Statistical analysis did not find any correlation between PC stage and DM treatments. Conclusions: Anti-diabetic medications that increase exposure to endogenous insulin do not appear to accelerate PC development as measured by the age of PC diagnosis or stage. These findings suggest that avoidance of certain drug classes used in DM treatments based on concerns for accelerating the presentation of PC are unjustified.