JOURNAL ARTICLE
REVIEW

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

Erika L Kleppinger, Kristen Helms
Annals of Pharmacotherapy 2007, 41 (5): 824-32
17456545

OBJECTIVE: To highlight the role of incretin hormones in the management of type 2 diabetes mellitus with a focus on vildagliptin, a dipeptidyl peptidase IV (DPP 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 vildagliptin, 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 manufacturer.

STUDY SELECTION AND DATA EXTRACTION: Articles pertaining to the pharmacology, pharmacokinetics, safety, and efficacy of vildagliptin 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 decreases 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 vildagliptin doses ranging from 25 mg daily to 100 mg twice daily, researchers observed consistent reductions in fasting plasma glucose, 4 hour postprandial glucose, and hemoglobin A1c. 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.

CONCLUSIONS: Vildagliptin represents a safe and effective new approach to targeting GLP-1 deficiencies in patients with type 2 diabetes by inhibiting DPP IV.

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