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

Abstract

The incidence of type 2 diabetes mellitus (T2DM) among children and adolescents has been rising. This condition is associated with obesity, and the prevalence is higher among minority or female youth. Lifestyle modification including diet and exercise is only successful in a small portion of the patients; therefore, pharmacotherapy approaches are needed to treat T2DM among youth. Currently, in the United States, only metformin and insulin are approved for the treatment of T2DM in children. Several antihyperglycemic agents including exenatide, glimepiride, glyburide, liraglutide, pioglitazone and rosiglitazone are also used off-label in this population. Moreover, several clinical trials are ongoing that are aimed to address 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 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 occurrence of additional conditions such as obesity and fatty liver disease. This manuscript reviews the prevalence of obesity and T2DM in children and adolescents (youth). We have then summarized published studies on safety and effectiveness of antihyperglycemic medications in youth. Drug disposition may be affected by age or puberty thus the expression and activity of different pathways for drug metabolism and xenobiotic transporters will be compared between youth and adults followed by summarizing pharmacokinetics studies of antihyperglycemic agents currently used in this population.