Kautzky-Willer, A.,Thurner, S.,limek, P.

Aim. There is firm evidence of a relation between type 2 diabetes (T2DM) and increased risks of cancer at various sites, but it is still unclear how different antihyperglycaemic therapies modify site-specific cancer risks. The aim of this study was to provide a complete characterization of all possible associations between individual T2DM therapies, statin use and site-specific cancers in the Austrian population. Methods. Medical claims data of 1 847 051 patients with hospital stays during 2006-2007 were used to estimate age-and sex-dependent co-occurrences of site-specific cancer diagnoses and treatment with specific glucose-lowering drugs and statins. Results. Patients treated with insulin or insulin secretagogues showed up to ninefold increased risks for cancers of the colon [males only (m)], liver (m), pancreas, lung (m) and brain (m), as well as a strongly decreased risk for prostate cancer (m). In patients taking statins, the risks were generally decreased, with a greater risk reduction in patients not receiving antihyperglycaemic therapies. The strongest effects were observed for use of insulin and pancreatic cancer [m: OR 4.5, 95% CI: 3.1-6.6; females (f): OR 4.2, 95% CI: 2.5-7.1], sulfonylureas (m: OR 2.8, 95% CI: 1.7-4.6; f: OR 3.0, 95% CI: 2.1-4.2) or glitazones and skin cancer (f: OR 0.54, 95% CI: 0.36-0.80), as well as metformin and cancer of the prostate (m: OR 0.82, 95% CI: 0.75-0.91) and corpus uteri (f: OR 1.7, 95% CI: 1.4-2.0) and non-Hodgkin's lymphoma (f: OR 0.76, 95% CI: 0.64-0.91). Conclusions. The use of statins offsets insulin-related cancer risks in patients with diabetes independently of sex and age. Overall, our data support the hyperglycaemia-cancer hypothesis. A reduction in endogenous or exogenous hyperinsulinaemia may be beneficial for cancer prevention. Therefore, insulin-sparing and insulin-sensitizing drugs should be the preferred treatment choices.