A medical device system and related method of automatically adjusting parameters of an insulin delivery controller of an insulin infusion device are disclosed. The methodology obtains therapy-related data associated with operation of the insulin infusion device for a number of days in the past, including sensor glucose data associated with glucose levels of the user, and meal data associated with identified meals. The obtained therapy-related data is processed to generate a suitable pharmacokinetic/pharmacodynamic (PK/PD) model of the user, wherein the PK/PD model fits at least some of the sensor glucose data obtained for the user. The PK/PD model can be used to calculate at least one adjusted parameter of the insulin delivery controller, based on additional therapy-related data associated with further operation of the insulin infusion device. The insulin delivery controller can be instructed or controlled to adjust its settings in accordance with the model-calculated parameters.