(P-486) Diabetes Medication Use Is Associated with Higher Grade and Increased Probability of Muscle-invasive Tumour Disease in Patients with Urothelial Carcinoma

Background: Observational studies indicate a potential association between diabetes and aggressiveness of bladder cancer.

Objectives: To determine the association between diabetes medication use and urothelial carcinoma (UC) characteristics at diagnosis. It is hypothesised that hyperinsulinemia can influence tumour growth and progression through the IGF-1 pathway.

Methods: A historic cohort study among UC patients was performed for which two large linked registries were used; namely PHARMO’s Out-patient Pharmacy Database and the Netherlands Comprehensive Cancer Organisation (IKNL) database. Patients diagnosed with, first time cancer, UC between 2000 and 2016 were included in this study. UC Patients with diabetes medication were matched on age and sex with subjects not using diabetes medication (ratio 1:2), resulting in 1,164 users of diabetes medication and 2,318 non-users. Multinomial logistic regression analysis was performed to compare cancer characteristics between different types of diabetes medication users (metformin, sulfonylureas and a combination) to non-users. Cancer characteristics studied are tumor invasiveness, tumor differentiation and cancer stage at time of diagnosis.

Results: Noninsulin antidiabetic drugs (NIAD) use was associated with an invasive type of UC compared to non-users (OR=1.39, 95%CI: 1.14-1.68 for T2+ versus Ta) as well as a poorly differentiated tumour (OR=1.35, 95%CI: 1.10-1.66 for poorly versus well differentiated tumours), especially for combined use of metformin and sulfonylureas (OR=1.41, 95%CI: 1.09-1.83 comparing T2+ to Ta and OR=1.58, 95% CI: 1.25-2.00 comparing poorly versus well differentiated tumours).

Conclusions: In UC patients, diabetes medication usage may be associated with a more aggressive tumour compared to no diabetes medication use at time of diagnosis as appears from this large registry study. However, residual confounding cannot be disregarded due to the retrospective nature of this study. Additionally, future studies require information on glycaemic control and lifestyle factors such as smoking to be able to substantiate the observed associations.