Glucose-lowering medications and the risk of cancer: a methodological review of studies based on real-world data.

AIM: Recent years have witnessed a proliferation of observational research examining the association between glucose-lowering medications and cancer, paired with an increasing concern on the quality of the produced evidence. Our objective was to review published studies in this area to identify the most common methodological challenges and sources of bias.

METHODS: We systematically searched PubMed to identify observational studies on glucose-lowering medications and cancer published between January 2000 and January 2016. We assessed the design and analytical methods used in each study, with a focus on their ability to achieve study validity, and further evaluated the prevalence of major methodological choices over time.

RESULTS: Out of 155 studies evaluated, only 26% implemented a new user design, 41% used an active comparator, 33% implemented a lag or latency period, 51% adjusted for diabetes duration. Potential for immortal person-time bias was identified in 63% of the studies; 55% of the studies adjusted for variables measured during the follow-up without appropriate statistical methods. Aside from a decreasing trend in adjusting for variables measured during the follow-up, we observed no trends in methodological choices over time.

CONCLUSIONS: The prevalence of well-known design and analysis flaws that may lead to biased results remains high among observational studies on glucose-lowering medications and cancer, limiting the conclusions that can be drawn from these studies. Avoiding known pitfalls could substantially improve the quality and validity of real-world evidence in this field. This article is protected by copyright. All rights reserved.