AIMS/HYPOTHESIS: Adherence to glucose-lowering drug (GLD) treatment regimens is crucial for metabolic control and improving prognosis. Because a diagnosis of cancer might have an impact on adherence to medication, this study explored changes in adhrence to GLDs following a cancer diagnosis. METHODS: All new users of GLDs between 1998 and 2011 who lived in the Eindhoven Cancer Registry-PHARMO Database Network catchment area were selected. Those with a primary cancer diagnosis during follow-up wereconsidered cases and matched with eligible controls without cancer during follow-up. Medication possession ratio (MPR) was used as indicator for medication adherence. Segmented linear auto-regression analysis with interrupted time series was used to assess changes in MPR for cases compared with controls (i.e. overall trend) due to (any) cancer diagnosis and specific cancer types. RESULTS: From the 52,228 GLD users selected, 3,281 cases with cancer and 12,891 controls without cancer during follow-up wereincluded in the study. In our analyses, before cancer diagnosis the MPR increased by 0.10% per month (95% CI 0.10, 0.10). Besides a significant drop in MPR at the time of cancer diagnosis of -6.3% (95% CI -6.5, -6.0), there was an ongoing, yet lower, monthly decline in MPR (-0.20%; 95% CI -0.21, -0.20) after cancer diagnosis. The largest drops in MPR at the time of cancer diagnosis, in the range of 11-15%, were seen among patients with stage IV disease and gastrointestinal or pulmonary cancers. CONCLUSIONS/INTERPRETATION: Our findings indicate a clear decline in adherence to GLD treatment regimens following a cancer diagnosis. The reason for the decline in MPR needs to be further elucidated.