Diabetes treatments and cancer risk: the importance of considering aspects of drug exposure.

Investigations of the association between diabetes, diabetes treatments, and cancer risk have raised several epidemiological challenges. In particular, a patient's exposure to glucose-lowering drugs needs to be represented accurately to allow unbiased assessment of the link between the treatments and cancer risk. Many studies have used a simple binary contrast (exposure to a specific drug vs no exposure), which has potentially serious drawbacks. In addition, methods used to determine the duration and cumulative dose of drug exposure differ widely between studies. In this Review, we discuss representation of drug exposure in pharmacoepidemiological investigations of the connection between diabetes drugs and cancer risk. We identify principles that might improve future research (particularly in observational studies), and consider issues related to reverse causation and detection bias.