These and other studies gave impetus to the clinical development of the inhibitors of DPP-4 for diabetes therapy, and in a pivotal proof-of concept study by Ahren and coworkers in 2004, vildagliptin, developed by researchers at Novartis, showed hemoglobin A1c improvements to target levels of 7% in a 1-year trial, whereas a significant rise was observed in the placebo group (103). Here, DPP4 is linked to diabetes mellitus.