Dipeptidyl peptidase 4 inhibitors

Dipeptidyl peptidase 4 inhibitors

Dipeptidyl peptidase 4 (DPP-4) inhibitors, such as sitagliptin and vildagliptin have their effect in the incretin regulation: they inhibit the metabolism of different peptides including GLP-1, thereby keeping up an adequate active incretin concentration. As a result, sitagliptin stimulates insulin secretion (1) and reduces glucagon release (2). Similar to incretin mimetics, clinical studies show significant lowering of the HbA1c, plasma glucose levels (postprandial and sober), and improved β-cell function.

Sitagliptin is indicated for DM2 patients in order to improve their glycemic control after combination therapy with metformin or a thiazolidinedione, diet and exercise has failed. The advantage of DPP-4 inhibitors over incretin mimetics is their oral administration.


The adverse effects of sitagliptin are mild. In combination with metformin, nausea is common; with thiazolidinedione, hypoglycemia and edema often occur.

One should notice, that only short studies have been performed and long term adverse effects are not known yet. Indeed, there is a point of concern regarding the inhibition of DPP-4, since this enzyme metabolises a lot of other peptides as well including neuropeptides, insulin-like growth factor and immunopeptides.

EPAR of sitagliptin.