DiaPep277 is an immunomodulatory peptide that arrests beta cell destruction in mouse models of type 1 diabetes mellitus (T1DM). This article extends an original pilot observation to two studies of 61 patients (age > 16 years), diagnosed with T1DM within 6 months, and with measurable beta cell function. Patients were treated with placebo (n = 27) or 1.0 mg DiaPep277 (n = 34). After 13 months, 1.0 mg Dia Pep277 treatment significantly (P = 0.02) preserved beta cell function as compared to the control with a trend for reduced HbA1c. This was achieved without an increase in insulin dose in the DiaPep277 group and with excellent safety. DiaPep277-treated patients also had fewer Th1 DiaPep277-specific T cells.