Vildagliptin | place in therapy review Table 8 | Effects of vildagliptin on body weight (all level 2 evidence) Design Double-blind RCT, 52 weeks Double-blind, placebo- controlled RCT, 24 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 Treatment and dose V 50 mg bid (n=526) M 1 g bid (n=254) Placebo + P 45 mg qd (n=138) V 50 mg qd + P 45 mg qd (n=124) V 50 mg bid + P 45 mg qd (n=136) 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 At 12 weeks: extension) Placebo –0.5 V 50 mg qd (n=56, of whom 42 completed V –0.4 extension) Extension phase: All patients were also taking stable doses Placebo –0.2 of metformin 1.5–3.0 g/day V –0.2 (P values NR) Placebo (n=19) Placebo +0.12 V 100 mg qd (n=18) V +0.21 NSD vs placebo Mean change from baseline in body weight (kg) Reference V 50 mg bid +0.3 M 1 g bid –1.9 (P<0.001 vs V) V 50 mg qd + P 45 mg qd +0.1a V 50 mg bid + P 45 mg qd +1.3 (P=0.003 vs placebo)a Placebo –0.73 V 25 mg bid +0.05 V 25 mg qd –0.55 V 50 mg qd +0.04 V 100 mg qd –0.07 All V doses NSD vs placebo Schweizer et al. 2007 Garber et al. 2007b Ristic et al. 2005 Ahrén et al. 2004a Ahrén et al. 2004b aChange versus placebo + P. bid, twice daily; M, metformin; NR, not reported; NSD, not statistically significantly different; P, pioglitazone; qd, once daily; RCT, randomized controlled trial; V, vildagliptin. infection in 6.8%, compared with 7.3% and 8.0%, respectively, with comparator. Mild to moderate hypoglycemia occurred with the same frequency in patients taking vildagliptin (1.4%) or comparator drugs (1.2%) (Amori et el. 2007). Liver function A pooled analysis of clinical trial data from more than 8000 patients was submitted by the manufacturer to European regulatory authorities in November 2007 following concerns over liver function with vildagliptin. Elevations more than three times the upper limit of normal levels of aspartate aminotransferase and alanine aminotransferase were revealed in 0.86%, 0.34%, and 0.21% of patients taking vildagliptin 100 mg once daily, 50 mg twice daily, and 50 mg once daily, respectively (Anon 2007). The corresponding rates were 0.20% in approximately 4400 patients receiving metformin, a thiazolidinedione, a sulfonylurea, or placebo, and 0.40% for placebo alone. Resource utilization Type 2 diabetes is a disease with a high social and economic cost, and is steadily increasing in prevalence (see Disease overview section). The bulk of this cost is attributable to the complications of diabetes. As discussed earlier, intensive control of blood glucose increases short-term costs compared with conventional management, but may reduce the long-term complication rate. 26 This reduction in complications should offset the additional cost of intensive blood glucose management. A new antidiabetic agent that achieves better glycemic control, and in turn lowers complication rates, would have the potential to make significant savings in the total resource utilization for diabetes management. Economic evidence for vildagliptin is not currently available and its effect on healthcare resources has not been assessed. Vildagliptin has shown some evidence of improved glycemic control (measured by HbA1c) compared with placebo, either as monotherapy or as an add-on to metformin (Tables 3 and 4). The magnitude of the reduction in HbA1c demonstrated by the evidence so far is up to 1 percentage point (Tables 3 and 4), comparable to that achieved with other oral glucose- lowering drugs. Vildagliptin improves beta-cell function (Table 6) and insulin sensitivity (Table 7), which in turn improves control of blood glucose. In theory, since vildagliptin acts by enhancing the physiologic response to ingestion of a meal, it may provide finer control of blood glucose than is possible with agents such as sulfonylureas or insulin that act more directly. There is evidence that glycemic control is maintained in the long term (52 weeks) with vildagliptin used as monotherapy or in combination with metformin (Ahrén et al. 2004a; Schweizer et al. 2007). Successful long-term glycemic control is an important clinical benefit, as it should contribute to a lower risk of complications, but this needs to be confirmed by further studies. © 2008 Core Medical Publishing Limited