Aims/hypothesis Type 2 diabetes is difficult to manage in patients with a long history of disease requiring insulin therapy. Moreover, addition of most currently available oral antidiabetic agents increases the risk of hypoglycaemia. Vildagliptin is a dipeptidyl peptidase-IV inhibitor, which improves glycaemic control by increasing pancreatic beta cell responsiveness to glucose and suppressing inappropriate glucagon secretion. This study assessed the efficacy and tolerability of vildagliptin added to insulin therapy in patients with type 2 diabetes. Materials and methods This was a multicentre, 24-week, double-blind, randomised, placebo-controlled, parallelgroup study in patients with type 2 diabetes that was inadequately controlled (HbA 1c =7.5-11%) by insulin. Patients received vildagliptin (n=144; 50 mg twice daily) or placebo (n=152) while continuing insulin therapy.Results Baseline HbA 1c averaged 8.4 ± 0.1% in both groups. The adjusted mean change from baseline to endpoint (AMΔ) in HbA 1c was −0.5±0.1% and −0.2± 0.1% in patients receiving vildagliptin or placebo, respectively, with a significant between-treatment difference (p=0.01). In patients aged ≥65 years, the AMΔ HbA 1c was −0.7±0.1% in the vildagliptin group vs −0.1±0.1% in the placebo group (p<0.001). The incidence of adverse events was similar in the vildagliptin (81.3%) and placebo (82.9%) groups. However, hypoglycaemic events were less common (p<0.001) and less severe (p<0.05) in patients receiving vildagliptin than in those receiving placebo. Conclusions/interpretation Vildagliptin decreases HbA 1c in patients whose type 2 diabetes is poorly controlled with high doses of insulin. Addition of vildagliptin to insulin therapy is also associated with reduced confirmed and severe hypoglycaemia. ClinicalTrials.gov ID no.: NCT 00099931.

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.

OBJECTIVE -To compare the efficacy and tolerability of vildagliptin and rosiglitazone during a 24-week treatment in drug-naïve patients with type 2 diabetes.RESEARCH DESIGN AND METHODS -This was a double-blind, randomized, active-controlled, parallel-group, multicenter study of 24-week treatment with vildagliptin (100 mg daily, given as equally divided doses; n ϭ 519) or rosiglitazone (8 mg daily, given as a once-daily dose; n ϭ 267).RESULTS -Monotherapy with vildagliptin and rosiglitazone decreased A1C (baseline ϭ 8.7%) to a similar extent during the 24-week treatment, with most of the A1C reduction achieved by weeks 12 and 16, respectively. At end point, vildagliptin was as effective as rosiglitazone, improving A1C by Ϫ1.1 Ϯ 0.1% (P Ͻ 0.001) and Ϫ1.3 Ϯ 0.1% (P Ͻ 0.001), respectively, meeting the statistical criterion for noninferiority (upper-limit 95% CI for between-treatment difference Յ0.4%). Fasting plasma glucose decreased more with rosiglitazone (Ϫ2.3 mmol/l) than with vildagliptin (Ϫ1.3 mmol/l). Body weight did not change in vildagliptin-treated patients (Ϫ0.3 Ϯ 0.2 kg) but increased in rosiglitazone-treated patients (ϩ1.6 Ϯ 0.3 kg, P Ͻ 0.001 vs. vildagliptin). Relative to rosiglitazone, vildagliptin significantly decreased triglycerides, total cholesterol, and LDL, non-HDL, and total-to-HDL cholesterol (Ϫ9 to Ϫ16%, all P Յ 0.01) but produced a smaller increase in HDL cholesterol (ϩ4 vs. ϩ9%, P ϭ 0.003). The proportion of patients experiencing an adverse event was 61.4 vs. 64.0% in patients receiving vildagliptin and rosiglitazone, respectively. Only one mild hypoglycemic episode was experienced by one patient in each treatment group, while the incidence of edema was greater with rosiglitazone (4.1%) than vildagliptin (2.1%).CONCLUSIONS -Vildagliptin is an effective and well-tolerated treatment option in patients with type 2 diabetes, demonstrating similar glycemic reductions as rosiglitazone but without weight gain.