Het gebruik van incretines en het risico op alvleesklierkanker: Een populatiegebaseerde cohortstudie

OBJECTIVE: To determine the association between the use of incretin agents and the risk of pancreatic Cancer. Incretins (dipeptidyl peptidase 4 [DPP-4] inhibitors and glucaconlike peptide 1 [GLP-1] receptor analogues] are effective new agents for the treatment of type 2 diabetes mellitus (T2DM). Incretins have been associated with pancreatic Cancer, but evidence is limited and conflicting. DESIGN AND METHODS: A retrospective population-based cohort study was conducted using data from the UK Clinical Practice Research Datalink (CPRD, 2007-2012). 182.428 adult patients with at least one non-insulin antidiabetic drug INIAD] prescription were matched to non-diabetic controls. Multivariable Cox proportional hazard ratios (HRa) and 95% confidence intervals (CI95) were used to estimate the risk of pancreatic Cancer in incretin users (N = 28,3701 as compared to controls and to other NIAD users. Adjustments were made for lifestyle, disease and drug history. In a sensitivity analysis, a new user design was used. RESULTS: The main duration of follow up was 4.1 years for incretin users. Current NIAD use was associated with a 4-fold increased risk of pancreatic Cancer and this risk almost doubled among current incretin users as compared to controls. Incretin use was not associated with pancreatic Cancer when compared to diabetic controls (HRa 1.36; CI95 0.94-1.961. However, the new user design did show an association between incretin use and pancreatic Cancer. CONCLUSION: Incretin use was not associated with pancreatic Cancer after adjustment for the severity of the underlying T2DM. The presence of confounding by disease severity and the lack of duration of use relationship do not support a causal explanation for the association between incretin agents and pancreatic Cancer.