A novel approach to support evidence-based medicine: should sulfonylureas remain an acceptable therapy for diabetes?
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A key element in evidence-based medicine approaches is the ability for clinicians to evaluate the scientific rigor and relevance of research evidence. In the treatment of diabetes, clinicians make increasingly difficult decisions about which drug regimens are best for their patients with limited evidence-based information. While the consensus is that metformin should be the initial drug treatment when diet and exercise are not sufficient, clinicians disagree on whether sulfonylureas should remain a suitable therapy after metformin. While this would be improved with further research investigating the comparative safety of therapeutic options, there is also need for better ways to synthesize available information to guide evidence-based decision-making in health services research. Study 1 summarizes the pre-existing evidence on the long-term safety risks associated with sulfonylurea therapy relative to other drug classes. Results from a series of meta-analyses provide some evidence that sulfonylureas are associated with elevated all-cause mortality and cardiovascular risks relative to several other medications, either as a monotherapy or in combination with metformin. Study 2 analyzes the comparative safety of second-line treatment in diabetic patients in the Veterans Health Administration to address gaps in the literature. Results suggest that second-line use of sulfonylureas is associated with increased risks compared to thiazolidinediones. Results also suggest that changes to existing metformin therapy may lead to differential hazards. Clinicians may disagree about the quality of the evidence as well as the relevancy to their own treatment population. Improvements in methods for evidence-based medicine that take this into account are needed. Study 3 applies an underutilized research method that allows for a more thoughtful synthesis of all available evidence. This framework allows clinicians to incorporate the scientific rigor and relevancy of previous study results when integrating new data into their current knowledge base. Results suggest an elevated risk in all models for sulfonylureas compared to thiazolidinediones and highlight the need to design more focused research to support clinical decision-making around medication safety. This novel application to evidence synthesis shows promise as applied to a health services research problem and has potential as a useful framework in other health services research areas.