Kaixin Zhou, Helle Krogh Pedersen, Adem Y. Dawed, Ewan R. Pearson
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Pharmacogenomics in diabetes mellitus: insights into drug action and drug discovery
Pharmacogenomics, the study of how genes influence drug response, has become an increasingly important technique in modern drug discovery. In this Review, Zhou and colleagues discuss the role of pharmacogenomics in the variability of antidiabetic drug action and how this knowledge can be used to target treatment and guide future drug development. Genomic studies have greatly advanced our understanding of the multifactorial aetiology of type 2 diabetes mellitus (T2DM) as well as the multiple subtypes of monogenic diabetes mellitus. In this Review, we discuss the existing pharmacogenetic evidence in both monogenic diabetes mellitus and T2DM. We highlight mechanistic insights from the study of adverse effects and the efficacy of antidiabetic drugs. The identification of extreme sulfonylurea sensitivity in patients with diabetes mellitus owing to heterozygous mutations in HNF1A represents a clear example of how pharmacogenetics can direct patient care. However, pharmacogenomic studies of response to antidiabetic drugs in T2DM has yet to be translated into clinical practice, although some moderate genetic effects have now been described that merit follow-up in trials in which patients are selected according to genotype. We also discuss how future pharmacogenomic findings could provide insights into treatment response in diabetes mellitus that, in addition to other areas of human genetics, facilitates drug discovery and drug development for T2DM.
期刊介绍:
Nature Reviews Endocrinology aspires to be the foremost platform for reviews and commentaries catering to the scientific communities it serves. The journal aims to publish articles characterized by authority, accessibility, and clarity, enhanced with easily understandable figures, tables, and other visual aids. The goal is to offer an unparalleled service to authors, referees, and readers, striving to maximize the usefulness and impact of each article. Nature Reviews Endocrinology publishes Research Highlights, Comments, News & Views, Reviews, Consensus Statements, and Perspectives relevant to researchers and clinicians in the fields of endocrinology and metabolism. Its broad scope ensures that the work it publishes reaches the widest possible audience.