Systems pharmacology modeling in type 2 Diabetes Mellitus

Abstract

This chapter provides an introduction to quantitative systems pharmacology (QSP) modeling of type 2 diabetes mellitus (T2DM). For practical reasons, biological scope is limited to those factors which determine glucose homeostasis as is commonly determined in 12-week, Phase 2 intervention trials via measurements of glycated hemoglobin (HbA1c). A review of information essential to a QSP effort in T2DM is provided. This includes a biological overview of the physiology and pathophysiology of glucose regulation along with the pharmacology of therapeutically relevant mechanisms of intervention. Literature References of use in quantifying key physiological and therapeutic effects are provided in this context. Although an explicit QSP model of T2DM is not provided, diagrams representing key pathways and organs are included along with an outline of the requisite steps in constructing such a model. Finally, two illustrative case examples of QSP model application in both preclinical and clinical pharmaceutical research are provided.