The role of vildagliptin in the management of type 2 diabetes mellitus

OBJECTIVE: To highlight the role of incretin hormones in the management of type 2 diabetes mellitus with a focus on vidagliptin, a dipeptidyl peptidase IV (DDP IV) inhibitor currently in development. DATA SOURCES: Searches were conducted in MEDLINE (1950-April 2007) and International Pharmaceutical Abstracts (1970-April 2007) using the key words vidagliptin, LAF237, and dipeptidyl peptidase IV inhibitor. Additional data were obtained from abstracts presented at the American Diabetes Association Scientific Sessions (2003-2006) and from the maufacturer. STUDY SELECTION AND DATA EXTRACTION: Articles pertaining to the pharmacology, pharmacokinetics, safety, and efficacy of vidagliptin for the treatment of type 2 diabetes were reviewed for inclusion. When available, human trials were included over animal studies. DATA SYNTHESIS: Reduced incretin effect is thought to be associated with type 2 diabetes. Glucagon-like peptide-1 (GLP-1), an incretin hormone, stimulates postprandial insulin release; however, it is rapidly degraded by DPP IV. Studies evaluating the use of vildagliptin in patients with type 2 diabetes found significant in DPP IV and increased GLP-1 activity 45 minutes after dosing. Glucagon levels were reduced, with little to no change in insulin levels. With vidagliptin loses ranging from 25 mg daily to 100 mg twice daily, researchers observed consistent reductions in fasting plasma glucose, 4 hour postprandial glucose, and hemoglobin A(1c). Similar benefits were seen when vildagliptin was used in combination with metformin. Vildagliptin was well tolerated after 12 weeks; however, incidences of hypoglycemia increased with longer study duration. Optimal results with minimal adverse effects were achieved with 25 mg twice daily and 50 mg once daily doses. CONCLUSION: Vildagliptin represents a safe and effective new approach to targeting GLP-1 deficiencies in patients with type 2 diabetes by inhibiting DPP IV.