Clinical Pharmacokinetics

, Volume 56, Issue 6, pp 561–571 | Cite as

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

  • Fatemeh AkhlaghiEmail author
  • Kelly L. Matson
  • Amir Hooshang Mohammadpour
  • Meghan Kelly
  • Asieh Karimani
Review Article


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.


Metformin Rosiglitazone Pioglitazone Liraglutide Exenatide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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

Compliance with Ethical Standards


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

Conflicts of interest

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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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical SciencesUniversity of Rhode IslandKingstonUSA
  2. 2.Department of Pharmacy PracticeUniversity of Rhode IslandKingstonUSA
  3. 3.Pharmaceutical Research CenterMashhad University of Medical SciencesMashhadIran

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