Hypoglycemia is a common complication among type 2 diabetes mellitus (T2DM) patients receiving sulfonylurea therapy. The aim of this study was to determine if genetic contributions to sulfonylurea pharmacokinetics or pharmacodynamics substantially affect the risk of hypoglycemia in these patients. In a retrospective case–control study in European American patients with T2DM, we examined the potential association between CYP2C9 reduced-function variants and sulfonylurea-related hypoglycemia. We also explored the relationship between sulfonylurea-related hypoglycemia and several candidate genetic variants previously reported to alter the response to sulfonylureas. We detected no evidence of association between CYP2C9 reduced-function alleles or any of the candidate genetic variants and sulfonylurea-related hypoglycemia. In conclusion, we identified no clinically significant predictors of hypoglycemia among genes associated with sulfonylurea pharmacokinetics or pharmacodynamics.
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This work was supported by National Institutes of Health grants R01GM109145 and R35GM131770. VKK is supported by K23GM117395. The datasets used for the analyses described were obtained from Vanderbilt University Medical Center resources, BioVU, and the Synthetic Derivative, which are supported by institutional funding, private agencies, and federal grants. These include the NIH funded Shared Instrumentation Grant S10RR025141; CTSA grants UL1TR002243, UL1TR000445, and UL1RR024975.
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Mitchell, S.L., Leon, D.A.C., Chaugai, S. et al. Pharmacogenetics of hypoglycemia associated with sulfonylurea therapy in usual clinical care. Pharmacogenomics J (2020). https://doi.org/10.1038/s41397-020-0171-4