A model able to simultaneously characterize and simulate 24-hour glucose and insulin profiles following multiple meal tests was developed, extending an integrated glucose-insulin model for oral glucose tolerance tests that was previously published. The analysis was based on glucose and insulin measurements from 59 placebo-treated patients with type 2 diabetes. Circadian variations in glucose homeostasis were assessed on relevant parameters based on literature review. They were best described by a nighttime dip in insulin secretion between approximately 9 p.m. and 5 a.m. using a modulator function. The integrated glucose-insulin model has thus been shown to be applicable to real-life situations determined by multiple meals over the course of a day. This provides the basis for the analysis and simulation of long-term glucose and insulin data. The model may also prove useful for understanding antidiabetic drug actions and requirements in the context of circadian changes in glucose-insulin regulation.