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Biomedical Informatics Approaches to Identifying Drug-Drug Interactions: Application to Insulin Secretagogues.


ABSTRACT: Drug-drug interactions with insulin secretagogues are associated with increased risk of serious hypoglycemia in patients with type 2 diabetes. We aimed to systematically screen for drugs that interact with the five most commonly used secretagogues-glipizide, glyburide, glimepiride, repaglinide, and nateglinide-to cause serious hypoglycemia.We screened 400 drugs frequently coprescribed with the secretagogues as candidate interacting precipitants. We first predicted the drug-drug interaction potential based on the pharmacokinetics of each secretagogue-precipitant pair. We then performed pharmacoepidemiologic screening for each secretagogue of interest, and for metformin as a negative control, using an administrative claims database and the self-controlled case series design. The overall rate ratios (RRs) and those for four predefined risk periods were estimated using Poisson regression. The RRs were adjusted for multiple estimation using semi-Bayes method, and then adjusted for metformin results to distinguish native effects of the precipitant from a drug-drug interaction.We predicted 34 pharmacokinetic drug-drug interactions with the secretagogues, nine moderate and 25 weak. There were 140 and 61 secretagogue-precipitant pairs associated with increased rates of serious hypoglycemia before and after the metformin adjustment, respectively. The results from pharmacokinetic prediction correlated poorly with those from pharmacoepidemiologic screening.The self-controlled case series design has the potential to be widely applicable to screening for drug-drug interactions that lead to adverse outcomes identifiable in healthcare databases. Coupling pharmacokinetic prediction with pharmacoepidemiologic screening did not notably improve the ability to identify drug-drug interactions in this case.

SUBMITTER: Han X 

PROVIDER: S-EPMC5378621 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Biomedical Informatics Approaches to Identifying Drug-Drug Interactions: Application to Insulin Secretagogues.

Han Xu X   Chiang ChienWei C   Leonard Charles E CE   Bilker Warren B WB   Brensinger Colleen M CM   Li Lang L   Hennessy Sean S  

Epidemiology (Cambridge, Mass.) 20170501 3


<h4>Background</h4>Drug-drug interactions with insulin secretagogues are associated with increased risk of serious hypoglycemia in patients with type 2 diabetes. We aimed to systematically screen for drugs that interact with the five most commonly used secretagogues-glipizide, glyburide, glimepiride, repaglinide, and nateglinide-to cause serious hypoglycemia.<h4>Methods</h4>We screened 400 drugs frequently coprescribed with the secretagogues as candidate interacting precipitants. We first predic  ...[more]

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