Here, we investigate whether adding DPP-4 inhibition (MK626, a DPP-4 inhibitor with appropriate pharmacokinetic properties in mice) to a subtherapeutically low dose of monoclonal CD3 antibodies reverses diabetes in new-onset diabetic NOD mice and we provide insights in the mechanism of immunomodulation and β-cell repair/expansion by the combinatory immunotherapy. Here, DPP4 is linked to diabetes mellitus.