OBJECTIVES: This study explores changes in glucose lowering drug (GLD) use associated with cancer development and treatment among diabetic individuals. METHODS: New GLDs users (1998-2011) living in the ECR-PHARMO catchment area were selected (n=52,228). Those with a primary cancer diagnosis were considered cases (n=3,281) and matched with eligible controls without cancer during follow-up (n=12,891). Conditional logistic regression analysis was used to assess changes in GLD use, i.e. treatment drop and initiating insulin, for cases compared to controls due to specific cancer types in four time windows (3-6 and 0-3 months before cancer diagnosis; 0-3 and 3-6 months after cancer diagnosis). RESULTS: In the 3-6 months before cancer diagnosis, gastrointestinal and pancreas cancer were associated with higher odds of starting with insulin (OR 3.9;95%CI 1.3-12.1 and OR 4.9;95%CI 1.3-18.1). Colorectal (OR 3.4; 95%CI 1.4-8.4) and gastrointestinal (OR 13.6;95%CI 5.0-36.9) cancers were associated with increased odds of initiating insulin in the 3 months after cancer diagnosis. After this period, these odds were increased for breast (OR 4.6;95%CI 1.7-12.6) and pulmonary (OR 3.3;95%CI 1.2-9.1) cancers. Within all time windows odds of treatment drops were higher for patients with gastrointestinal cancers, while for all other cancers (except breast and prostate) odds were only higher after cancer diagnosis. CONCLUSIONS: Already 3 to 6 months before the diagnosis of gastrointestinal or pancreas cancer a higher odds of initiating insulin use was observed, suggesting reverse causation. Stopping GLDs was common after cancer diagnosis, while the diagnosis of most cancer types was associated with the start of insulin.