This trial (NCT00099866) is registered with ClinicalTrials.gov. AbstractAims To evaluate the ability of vildagliptin and metformin to sustain reductions in HbA 1c over a 1-year treatment period in drug-naïve patients with Type 2 diabetes (Type 2 DM).Methods Double-blind, randomized, multicentre, active-controlled, parallel-group study of 52-week treatment with vildagliptin (100 mg daily, n = 526) or metformin (titrated to 2000 mg daily, n = 254) in drug-naïve patients (baseline HbA 1c = 7.5-11.0%). HbA 1c was measured periodically over 1 year.Results Vildagliptin and metformin each rapidly decreased HbA 1c from an equal baseline of 8.7%. Most of the HbA 1c reduction was attained by week 12, and the efficacy was sustained throughout 1-year treatment with both agents. At the study end, significant HbA 1c reductions from baseline were seen with both vildagliptin (-1.0 ± 0.1%, P < 0.001) and metformin (-1.4 ± 0.1%, P < 0.001); however, statistical non-inferiority of 50 mg vildagliptin twice daily to 1000 mg metformin twice daily was not established. Body weight did not change during the 1-year treatment with vildagliptin (0.3 ± 0.2 kg, P = 0.17) and decreased in metformin-treated patients (-1.9 ± 0.3 kg, P < 0.001). The proportion of patients experiencing an adverse event was 70.1 vs. 75.4% in patients receiving vildagliptin and metformin, respectively. The proportion of patients experiencing a gastrointestinal adverse event was twofold higher in the metformin group, driven by a 3-4-fold greater incidence of diarrhoea, nausea and abdominal pain. The incidence of hypoglycaemia was similarly low in both groups ( < 1%).Conclusions A clinically meaningful decrease in HbA 1c that was sustained throughout a 1-year treatment in drug-naïve patients with Type 2 DM was seen with both metformin and vildagliptin monotherapy. Diabet. Med. 24, 955-961 (2007)

Aim: The aim of this study was to compare efficacy and tolerability of initial combination therapy with vildagliptin/ pioglitazone to component monotherapy. Methods: This 24-week, multicentre, randomized, double-blind, active-controlled study assessed the effects of the dipeptidyl peptidase-4 inhibitor vildagliptin (100 mg q.d.), pioglitazone (30 mg q.d.) and vildagliptin combined with pioglitazone (100/30 mg q.d. or 50/15 mg q.d.) in 607 drug-naive patients with type 2 diabetes (T2DM). The primary outcome measure was change from baseline in HbA 1c in patients receiving initial combination therapy compared with pioglitazone monotherapy. Results: After 24-week treatment, adjusted mean changes in HbA 1c from baseline (approximately 8.7%) in patients receiving pioglitazone monotherapy, 50/15 mg combination, 100/30 mg combination and vildagliptin monotherapy were ÿ1.4 AE 0.1%, ÿ1.7 AE 0.1%, ÿ1.9 AE 0.1% and ÿ1.1 AE 0.1% respectively. Both low-dose and high-dose combinations were significantly more efficacious than pioglitazone alone (p ¼ 0.039 and p < 0.001 respectively). Adjusted mean changes in fasting plasma glucose were ÿ1.9 AE 0.2, ÿ2.4 AE 0.2, ÿ2.8 AE 0.2 and ÿ1.3 AE 0.2 mmol/l respectively, and both combination groups were significantly more effective than pioglitazone monotherapy (p ¼ 0.022 and p < 0.001 respectively). The overall incidence of adverse events ranged from 45.8% in the low-dose combination to 51.6% in the pioglitazone monotherapy group. The incidence of peripheral oedema was highest in patients receiving pioglitazone monotherapy (9.3%) and lowest in those receiving low-dose combination (3.5%). One mild hypoglycaemic event was reported by one patient receiving high-dose combination and one patient receiving vildagliptin monotherapy. Conclusions: First-line treatment with vildagliptin/pioglitazone combination in patients with T2DM provides better glycaemic control than either monotherapy component yet has minimal risk of hypoglycaemia and a tolerability profile comparable with component monotherapy.

In patients with T2DM inadequately controlled with prior SU monotherapy, addition of vildagliptin (50 or 100 mg daily) to glimepiride (4 mg once daily) improves glycaemic control and is well tolerated. Addition of vildagliptin 50 mg daily to SU monotherapy may be a particularly attractive therapy in elderly patients.