The model-based Karlsburg Diabetes Management System (KADIS^®) has been developed as a patient-focused decision-support tool to provide evidence-based advice for physicians in their daily efforts to optimize metabolic control in diabetes care of their patients on an individualized basis. For this purpose, KADIS^® was established in terms of a personalized, interactive in silico simulation procedure, implemented into a problem-related diabetes health care network and evaluated under different conditions by conducting open-label mono- and polycentric trials, and a case–control study, and last but not least, by application in routine diabetes outpatient care. The trial outcomes clearly show that the recommendations provided to the physicians by KADIS^® lead to significant improvement of metabolic control. This model-based decision-support system provides an excellent tool to effectively guide physicians in personalized decision-making to achieve optimal metabolic control for their patients.