Head-to-head Study: ビルダグリプチン vs グリメピリド メトフォルミンへの追加投与(1年中間解析) Study purpose: to demonstrate long-term efficacy and safety of add-on therapy with vildagliptin vs glimepiride in patients with T2DM inadequately controlled with ongoing metformin monotherapy in a randomized, double-blind, multicenter study Interim analysis: to demonstrate non-inferiority of vildagliptin vs glimepiride at 1 year Target population: patients with T2DM inadequately controlled on a stable metformin monotherapy (metformin minimum dose 1500 mg/day; baseline HbA1c 6.5–8.5%) n=1396: ビルダグリプチン 50 mg 1日2回+ メトフォルミン N=2789* Metformin n=1393: グリメピリド 最大6 mg 1日1回+ メトフォルミン 1-year interim analysis 4 weeks Ferrannini E, et al. Diabetes Obes Metab. 11,2009,, 157 104 weeks Head-to-head Study: ビルダグリプチン vs グリメピリド メトフォルミンへの追加投与(1年中間解析) NI: 97.5% CI (0.02,0.16) Body Weight (kg) Vilda 50 mg bid + Met Glim up to 6 mg qd + Met −1.8 kg difference Time (Weeks) Time (Weeks) Incidence (%) n= Ferrannini E, et al. Diabetes Obes Metab. 11,2009,, 157 Patients with >1 Hypos (%) Number of Hypoglycemic Events (Grade 2 and Suspected Grade 2) 1389 1383 1389 1383 1389 1383 No. of Events Duration: 52 weeks Add-on to met: vilda vs glim Severe Events No. of Events Mean HbA1c (%) Between-group difference in adjusted mean change from BL at 52 weeks: 0.09% Vildagliptin 50 mg twice daily + metformin Glimepiride up to 6 mg once daily + metformin ビルダグリプチン 心・脳血管安全性評価 メタ解析(PⅢ-25試験 50mg qd N=1393 , 50mg bid N=6116) Incidences and Odds Ratios for Adjudicated CCV Events by Treatment Odds Ratio ・CCV events: ACS, TIA, Stroke, and CCV death ビルダグリプチン n / N (%) All comparators n / N (%) Vilda 50 mg qd 10/1393 (0.72) 14/1555 (0.90) 0.88 (0.37 - 2.11) Vilda 50 mg bid 81/6116 (1.32) 80/4872 (1.64) 0.84 (0.62 - 1.14) M-H RR(95% CI) 0.1 1 10 Vildagliptin better Vildagliptin worse Data were pooled from 25 Phase III studies of vildagliptin, used either as monotherapy or combination therapy, with durations of 12 weeks to ≥2 years. The safety of vildagliptin [50 mg qd (N = 1393) or 50 mg bid (N = 6116)] was assessed relative to a pool of all comparators [both placebo and active comparators (N = 6061)]. Diabetes, Obesity and Metabolism 2010 12: 485 ビルダグリプチンとグリメピリドの グルカゴンへの影響(2年間の検討) グルカゴン AUC0-2hr(pmol.hr/L) 5 4 3 2 1 0 ビルダグリプチン (n=137) グリメピリド -1 (n=121) -2 -3 -4 Baseline glucagon AUC0-2hr:66.6±2.3 pmol.hr/L -5 * P<0.001(vs グリメピリド) メトホルミンでコントロール不十分な2型糖尿病患者を対象に、グルカゴンへの影響をグリメピリドとビ ルダグリプチン50mg1日2回とで比較検討した。 Ahren B, et al. Diabetes Care 33:730–732, 2010