Diabetes mellitus is a chronic progressive metabolic disorder that has profound consequences for individuals,
families, and society. To date, main available oral antidiabetic medications target either insulin resistance (metformin,
glitazones), or insulin deficiency (sulfonylureas, glinides), but leading to shortfalls in medication. Advancement in
modern oral hypoglycemic agents may be encouraged with or in place of traditional therapies. The lower risk for
hypoglycemic events as compared with other insulinotropic or insulin-sensitizing agents make DPP-4 inhibitors very
promising candidates for a more physiological treatment of type-2 diabetes. Only some DPP-4 inhibitors are currently
used for the treatment of type 2 diabetes (T2DM) and various inhibitors currently undergoing animal and human testing.
A number of catalytically active DPPs distinct from DPP-4 (DPP II, FAP, DPP-8, and DPP-9) have been described that is
associated with side-effect and toxicity. To discover potent and selective and safer drugs in a shorter time frame and with
reduced cost it requires using an innovative approach for designing novel inhibitors. This review article focuses on the
status of advanced lead candidates of DPP group and their binding affinity with the active site residue of target structure
which help in discovery of potent and selective DPP-4 inhibitors by lead optimization approach.