Vildagliptin: a novel DPP-4 inhibitor with pancreatic islet enhancement activity for treatment of patients with type 2 diabetes.

Type 2 diabetes is now one of the most challenging health-care problems, and novel treatment strategies are required. The pancreatic islet dysfunction of type 2 diabetes involves problems with both insulin and glucagon since appropriate levels of both hormones are required for maintenance of glucose homeostasis. Enhancement of pancreatic function by incretins such as glucagon-like peptide (GLP)-1 is a new therapeutic approach. These incretins are inactivated by the enzyme dipeptidyl peptidase (DPP)-4. Vildagliptin is a potent, orally active, highly selective DPP-4 inhibitor that enhances the antidiabetic actions of the incretins. Pharmacokinetic studies showed that it is absorbed rapidly but has a sufficiently long period of action to require only once-daily dosing. Three phase II studies of vildagliptin use for 12 weeks in patients with type 2 diabetes have been reported. When vildagliptin was used either as monotherapy or combined with metformin, the treatment versus placebo resulted in significant reductions in hemoglobin (Hb)A(1c). The HbA(1c) was maintained during extended treatment over one year in the study of combination use with metformin. The studies indicated that the greater glycemic control appears to reflect an improvement in islet function. The improvement in glycemic control with vildagliptin was not associated with any body weight gain. Vildagliptin did not cause any clinically relevant changes in safety and was well tolerated. Therefore, further studies are being carried out on vildagliptin to assess long-term efficacy and safety in patients with type 2 diabetes.