Vildagliptin: a review of its use in type 2 diabetes mellitus.

Vildagliptin (Galvus®, Jalra®, Xiliarx®) is an orally administered dipeptidyl peptidase-4 (DPP-4) inhibitor. In patients with type 2 diabetes mellitus, vildagliptin 50 mg twice daily is indicated for use in combination with metformin or a thiazolidinedione, and vildagliptin 50 mg once daily is indicated for use in combination with a sulfonylurea. A fixed-dose combination of vildagliptin/metformin (Eucreas®, Icandra®, Zomarist®) is also available. This article reviews the clinical efficacy and tolerability of vildagliptin in patients with type 2 diabetes, as well as summarizing its pharmacological properties. The efficacy of monotherapy or combination therapy with oral vildagliptin in patients with type 2 diabetes has been examined in randomized, double-blind, multicentre trials. Monotherapy with vildagliptin 50 mg once or twice daily reduced glycosylated haemoglobin (HbA(1c)) from baseline to a significantly greater extent than placebo, according to the results of 12- to 52-week trials in patients with type 2 diabetes. In terms of the reduction from baseline in HbA(1c) seen in active comparator trials of 12-104 weeks' duration, the noninferiority of vildagliptin 50 mg twice daily was established versus acarbose or rosiglitazone, the noninferiority of vildagliptin 100 mg once daily (an off-label dosage) versus metformin was established in elderly patients and vildagliptin 50 mg twice daily was more effective than voglibose; however, the noninferiority of vildagliptin 50 mg twice daily versus metformin or gliclazide was not established in two other trials. Combination therapy with vildagliptin 50 mg twice daily plus metformin improved HbA(1c) to a significantly greater extent than monotherapy with metformin and/or vildagliptin alone in patients with type 2 diabetes whose disease was inadequately controlled by metformin monotherapy or who were treatment naive, according to the results of 12- or 24-week trials. In addition, vildagliptin 50 mg twice daily plus metformin demonstrated noninferiority to pioglitazone plus metformin, glimepiride plus metformin or gliclazide plus metformin in terms of the change from baseline in HbA(1c) after 24 or 52 weeks' therapy in patients with inadequately controlled type 2 diabetes. The addition of vildagliptin 50 mg twice daily to pioglitazone or vildagliptin 50 mg once daily to glimepiride improved HbA(1c) to a significantly greater extent than a thiazolidinedione or glimepiride alone in patients with type 2 diabetes whose disease was inadequately controlled, according to the results of 24-week trials. Oral vildagliptin 50 mg once or twice daily was generally well tolerated in patients with type 2 diabetes. In particular, vildagliptin was associated with a low risk of hypoglycaemia and was weight neutral. Increases in transaminase levels were sometimes observed with a vildagliptin dosage of 100 mg once daily in clinical trials, and liver function should be monitored in patients receiving vildagliptin. However, meta-analyses of clinical trial data suggested that vildagliptin 50 mg once or twice daily was not associated with an increased risk of hepatic adverse events, transaminase elevations ≥3 × the upper limit of normal, pancreatitis, cardiovascular or cerebrovascular events, infections or skin-related toxicity. In conclusion, vildagliptin is an important option for use in combination with metformin, a sulfonylurea or a thiazolidinedione in patients with type 2 diabetes who require combination therapy.