Bykov K, et al. - Via systematically searching PubMed, researchers identified relevant observational studies in which researchers reported on glucose-lowering medications and cancer published between January 2000 and January 2016. They evaluated the design and analytical methods used in each study, focusing on their ability to achieve study validity, and further assessed the prevalence of major methodological choices over time. Of the 155 studies assessed, only 26% implemented a new user design, 41% used an active comparator, 33% used a lag or latency period, and 51% adjusted for the duration of diabetes. Apart from a decreasing trend in adjustment for variables measured during the follow-up, they did not identify any trends in methodological choices over time. Overall, the prevalence of well-known design and analysis flaws that may result in biased outcomes remains high among glucose-lowering drug and cancer observational studies, limiting the conclusions that can be drawn from these studies. Avoiding known pitfalls in this field could significantly improve the quality and validity of real-world evidence.