Place in therapy review Vildagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus Louise Profit, Paul Chrisp, Carole Nadin Core Medical Publishing, Knutsford, UK Abstract Introduction: Type 2 diabetes is increasing in prevalence worldwide and is a leading cause of morbidity and mortality, mainly due to the development of complications. Vildagliptin is an inhibitor of dipeptidyl peptidase 4 (DPP-4), a new class of oral antidiabetic agents. Aims: To evaluate the role of vildagliptin in the management of type 2 diabetes. Evidence review: Clear evidence shows that vildagliptin improves glycemic control (measured by glycosylated hemoglobin and blood glucose levels) more than placebo in adults with type 2 diabetes, either as monotherapy or in combination with metformin. Vildagliptin is as effective as pioglitazone and rosiglitazone, and slightly less effective than metformin, although better tolerated. Further glycemic control is achieved when adding vildagliptin to metformin, pioglitazone, or glimepride. There is evidence that vildagliptin improves beta-cell function and insulin sensitivity. Vildagliptin does not appear to be associated with weight gain or with a higher risk of hypoglycemia than placebo or other commonly used oral antidiabetic agents. Economic evidence is currently lacking. Place in therapy: Vildagliptin improves glycemic control with little if any weight gain or hypoglycemia in adult patients with type 2 diabetes when given alone or in combination with metformin, thiazolidinediones, or sulfonylureas. Since many diabetic patients require combination therapy, the complementary mechanism of action of vildagliptin and other commonly prescribed antidiabetic drugs represents an important new therapeutic option in diabetes management. Core Evidence. 2008;3(1):13–30 doi: 10.3355/ce.2008.009 Key words: dipeptidyl peptidase IV (dipeptidyl peptidase 4) inhibition, glycemic control, LAF 237, type 2 diabetes, vildagliptin Core evidence place in therapy summary for vildagliptin 50 mg once or twice daily in adults with type 2 diabetes Evidence Implications Outcome measure Disease-oriented evidence Reduction in glycylated hemoglobin Reduction in fasting and postprandial plasma glucose Glycemic control in combination with metformin, pioglitazone, or glimepride Increase in postprandial GLP-1 Effects on postprandial insulin Improvement in beta-cell function Improvement in insulin sensitivity Patient-oriented evidence Hypoglycemia Weight gain Tolerability Liver function Economic evidence Cost effectiveness bid, twice daily; GLP-1, glucagon-like peptide. Clear Clear Clear Clear Substantial Clear Substantial Clear Clear Clear Limited No evidence Vildagliptin improves glycemic control more than placebo; 50 mg bid less effective than metformin 1 g bid; comparable to pioglitazone and rosiglitazone Greater reduction with vildagliptin than with placebo; more sustained effect than rosiglitazone Adding vildagliptin to metformin, thiazolidinediones, or sulfonylureas causes a further improvement in glycemic control Greater increase with vildagliptin than placebo Similar with vildagliptin and placebo. Implies improved insulin secretion and sensitivity, shown by no change in insulin with lower glucose Greater improvement with vildagliptin than placebo Greater improvement with vildagliptin than placebo Similar frequency with vildagliptin and placebo, and with metformin or thiazolidinediones Similar with vildagliptin and placebo; weight gain less than with thiazolidinediones, but greater than with metformin Well tolerated with few adverse effects; nasopharyngitis, cough, and headache Unpublished data reveal similar elevations in liver enzymes compared with metformin, a thiazolidinedione, a sulfonylurea, or placebo. Liver function tests necessary before and during treatment with vildagliptin, and the drug should not be used in patients with liver impairment Studies required to verify the impact of vildagliptin alone or in combination with other oral agents on costs of illness