Objectives: The goals of this study were to develop (1) a safe and effective protocol for the clinical control of type 1 diabetes using conventional self-monitoring blood glucose (SMBG) measurements and multiple daily injections with insulin analogues, and (2) an in silico simulation tool of type 1 diabetes to predict long-term glycemic control outcomes of clinical interventions. Methods: The virtual patient method was used to develop a simulation tool for type 1 diabetes using data from a type 1 diabetes patient cohort (n = 40). The tool was used to test the adaptive protocol (AC) and a conventional intensive insulin therapy (CC) against results from a representative control cohort. Optimal and suboptimal basal insulin replacements were evaluated as a function of SMBG frequency in conjunction with the (AC and CC) prandial control protocols. Results: In long-term glycemic control, the AC protocol significantly decreased hemoglobin A1c in conditions of suboptimal basal insulin replacement for SMBG frequencies =6/day, and reduced the occurrence of mild and severe hypoglycemia by 86–100% over controls, over all SMBG frequencies in conditions of optimal basal insulin.