Mean change from baseline in HbA1c (percentage points) % patients reaching HbA1c <7.0%a Outcome Reference Placebo NR V 47% Placebo 23% P values NR Placebo 10.7% V 41.7% P value NR V 25 mg bid 44% V 25 mg bid –0.44 V 25 mg qd 28% V 25 mg qd –0.30 V 50 mg qd 40% V 50 mg qd –0.97 V 100 mg qd 46% V 100 mg qd –0.95 Mean change from baseline in fasting plasma glucose (mmol/L) Placebo +0.23 V –0.9 (P=0.0043) Placebo –0.41 All doses NSD vs placebo Greater decrease with V than with placebo at 12 weeks (P=0.0057) Greater decrease with V than with placebo at 52 weeks (P=0.031) Placebo –0.4 V –1.1 (P=0.037) Placebo –0.3 V –1.0 (P<0.05) Greater decrease with V than placebo (P<0.05) NR Mean change from baseline in 4 h-postprandial plasma glucose (mmol/L) Placebo +0.2 V –1.7 (P<0.0001) Placebo –0.61 V 25 mg bid –1.03 V 25 mg qd –1.50 V 50 mg qd –2.00 (P=0.012 vs placebo) V 100 mg qd –1.50 All other doses NSD vs placebo Greater decrease with V than with placebo at 12 weeks (P<0.0001) Greater decrease with V than with placebo at 52 weeks (P=0.0001) Placebo –0.4 V –1.9 (P<0.001) NR NR NR NR Pratley et al. 2006; Pratley & Galbreath 2004 Ristic et al. 2005 Ahrén et al. 2004a Ahrén et al. 2004b Ahrén et al. 2003 Mari et al. 2005 Vildagliptin | place in therapy review ...table continued Design Treatment and dose Double-blind, placebo-controlled RCT, 12 weeks Double-blind, placebo-controlled, multicenter RCT, 12 weeks Double-blind, placebo-controlled, multicenter RCT, 12 weeks Optional extension for further 40 weeks Double-blind, placebo-controlled, multicenter RCT, 4 weeks Double-blind, placebo-controlled RCT, 4 weeks Double-blind, placebo-controlled, single center RCT, 4 weeks Placebo (n=28) V 25 mg bid (n=70) Placebo (n=58) V 25 mg bid (n=51) V 25 mg qd (n=54) V 50 mg qd (n=53) V 100 mg qd (n=63) Placebo (n=51, of whom 29 completed extension) V 50 mg qd (n=56, of whom 42 completed extension) All patients were also taking stable doses of M 1.5–3 g/day Placebo (n=19) Placebo (n=20) V 100 mg qd (n=20) Placebo (n=11) V 100 mg bid (n=9) Placebo –0.6 V –0.6 (P=0.0012) NR NR NR V 50 mg qd –0.56 (P=0.003 vs placebo) V 100 mg qd –0.53 (P=0.004 vs placebo) Other doses NSD vs placebo At 12 weeks: V –0.6 Placebo 0.1 (P<0.0001) In extension study: V +0.0128 per month Placebo +0.0656 per month (P=0.0243) Placebo –0.15 NR NR NR NR NR NR NR NR NR NR V 100 mg qd (n=18) V –0.53 (P<0.001) aOf patients with HbA1c ≥7.0% at baseline. bPlacebo subtracted value. cResults presented graphically, not stated. d2 h-postprandial plasma glucose. bid, twice daily; G, glimepiride; I, insulin; M, metformin; NR, not reported; NSD, not statistically significantly different; qd, once daily; RCT, randomized controlled trial; V, vildagliptin. Effects on blood glucose Most of the published evidence shows that vildagliptin 50 mg/day or 100 mg/day is more effective than placebo in reducing both fasting plasma glucose and 2 and 4 hours postprandial plasma glucose (Tables 3 and 4). In the dose-ranging study, the changes from baseline did not reach statistical significance compared with placebo (except for the change in 4 hours postprandial glucose with vildagliptin 50 mg once daily), but the numerical values were broadly consistent with a dose-related effect reaching a plateau at 50 or 100 mg/day (Ristic et al. 2005; Table 4). Between-group changes in fasting plasma glucose (FPG) with vildagliptin 50 and 100 mg/day (–0.8 and –1.7 mmol/L, respectively) and in 2 hours postprandial glucose (–1.9 and –2.3 mmol/L) also showed significant improvements compared with placebo in patients receiving metformin ≥1.5 g/day (Bosi et al. 2007). Vildagliptin caused a significantly smaller reduction in 22 © 2008 Core Medical Publishing Limited