Pharmacokinetic-Pharmacodynamic Modeling of Metformin for the Treatment of Type II Diabetes Mellitus

Abstract

Metformin is an antihyperglycemic agent commonly used for the treatment of Type II diabetes mellitus. However, its effects on patients are derived mostly from clinical experiments. In this current study, a dynamic model of metformin combined with a Type II diabetic physiological model is proposed. The metformin model is based on the pharmacokinetic and pharmacodynamic relationship with a human body. The Type II diabetic model is a modification of an existing compartmental diabetic model.  The corresponding model parameters are estimated by optimization using the clinical data from published reports. From the dynamic simulation, the combination treatment of insulin infusion plus oral metformin is shown to be superior than the monotherapy with metformin only. This result is consistent with clinical understanding of the use of metformin and insulin treatments. The model can be further analyzed for evaluating the treatment of diabetes mellitus with different pharmacological agents.