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Clinical Pharmacokinetics and Pharmacodynamics of Antihyperglycemic Medications in Children and Adolescents with Type 2 Diabetes Mellitus

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Abstract

The incidence of type 2 diabetes mellitus (T2DM) among children and adolescents has been rising. This condition is associated with obesity, and it's prevalence is higher among minority or female youth. Lifestyle modification including diet and exercise is only successful in a small proportion of patients; therefore, pharmacotherapy approaches are needed to treat T2DM among youth. Currently, in the USA, only metformin and insulin are approved for the treatment of T2DM in children. However, several antihyperglycemic agents including exenatide, glimepiride, glyburide, liraglutide, pioglitazone, and rosiglitazone are also used off-label in this population. Moreover, a number of clinical trials are ongoing that are aimed at addressing the safety and efficacy of newer antihyperglycemic agents in this population. Little is known about the safety, efficacy, or pharmacokinetics of antihyperglycemic agents in children or adolescents. Our ability to predict the pharmacokinetics of these agents in youth is hampered first by the lack of information about the expression and activity of drug-metabolizing enzymes and transporters in this population and second by the presence of comorbid conditions such as obesity and fatty liver disease. This article reviews the prevalence of obesity and T2DM in children and adolescents (youth). We then summarize published studies on safety and effectiveness of antihyperglycemic medications in youth. Drug disposition may be affected by age or puberty and thus the expression and activity of different pathways for drug metabolism and xenobiotic transporters are compared between youth and adults followed by a summary of pharmacokinetics studies of antihyperglycemic agents currently used in this population.

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Acknowledgements

Use of the University of Washington Drug Interaction Database is gratefully acknowledged.

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Authors and Affiliations

  1. Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Office 495 A, 7 Greenhouse Road, Kingston, RI, 02881, USA

    Fatemeh Akhlaghi & Meghan Kelly

  2. Department of Pharmacy Practice, University of Rhode Island, Kingston, RI, USA

    Kelly L. Matson

  3. Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Hooshang Mohammadpour & Asieh Karimani

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  1. Fatemeh Akhlaghi
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Correspondence to Fatemeh Akhlaghi.

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Support received from Grant # R15 GM101599 from the National Institutes of Health is gratefully acknowledged.

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Fatemeh Akhlaghi, Kelly L. Matson, Amir Hooshang Mohammadpour, Meghan Kelly, and Asieh Karimani declare that they have no conflicts of interest.

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Akhlaghi, F., Matson, K.L., Mohammadpour, A.H. et al. Clinical Pharmacokinetics and Pharmacodynamics of Antihyperglycemic Medications in Children and Adolescents with Type 2 Diabetes Mellitus. Clin Pharmacokinet 56, 561–571 (2017). https://doi.org/10.1007/s40262-016-0472-6

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