As part of an extensive clinical development programme in patients with type 2 diabetes (T2DM), vildagliptin 50 mg once daily and twice daily, and 100 mg once daily have been assessed in placebo-controlled and, more importantly, in head-to-head active-comparator monotherapy trials over a wide range of baseline HbA1c levels and in a large number of elderly patients. Notable findings in individual trials included: comparable HbA1c lowering over 24 weeks with 100 mg once daily or 50 mg twice daily; efficacy comparable to rosiglitazone with reduced risk of weight gain and oedema over 24 weeks; and durable glycaemic control for up to 2 years with a reduced frequency of gastrointestinal adverse events compared with metformin. Pooled monotherapy data indicate that vildagliptin 100 mg daily produces consistent and clinically meaningful reductions in HbA1c across a range of initial HbA1c levels, in patients with lower and greater body mass index, and in younger and older patients. To date, the safety/tolerability profile seems comparable to placebo with neutral effects on body weight and lipid profiles, and minimal risk of hypoglycaemia. A preliminary study in subjects with impaired glucose tolerance showed that vildagliptin 50 mg once daily enhanced islet cell function, reduced glycaemic excursions and was very well tolerated, paving the way for a future trial in diabetes prevention. Vildagliptin has also been extensively studied in multiple clinical scenarios as add-on combination therapy in patients with inadequate glycaemic control on metformin, thiazolidinedione, sulfonylurea and insulin treatment, and has consistently been shown to improve glycaemic control with good tolerability and low risk for hypoglycaemia. In a trial in patients receiving metformin, the addition of vildagliptin 50 mg twice daily resulted in a 1.1% reduction in HbA1c at 24 weeks. Compared with add-on pioglitazone 30 mg daily in patients inadequately controlled with ongoing metformin therapy, vildagliptin 50 mg twice daily reduced HbA1c by 0.9% vs. 1.0% and was not associated with weight gain (+0.3 kg vs. +1.9 kg) over 24 weeks. Most notably, vildagliptin plus pioglitazone as initial combination therapy in drug-naive patients resulted in robust HbA1c reductions of 1.9% from baseline. In patients receiving stable insulin therapy, vildagliptin 50 mg twice daily improved glycaemic control and was associated with a significant reduction in hypoglycaemic episodes over 24 weeks. Vildagliptin shows considerable promise as a partner for metformin and other commonly used oral antidiabetic agents, and may well play an important role in combination with insulin therapy to further improve glycaemic control.