Pratley Richard E, Reusch Jane E -B, Fleck Penny R, Wilson Craig A, Mekki Qais
Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine, Given C331, 89 Beaumont Avenue, Burlington, VT 05405, USA.
Curr Med Res Opin. 2009 Oct;25(10):2361-71. doi: 10.1185/03007990903156111.
To evaluate the efficacy and safety of alogliptin in patients with type 2 diabetes inadequately controlled by therapy with a thiazolidinedione (TZD).
In a multicenter, double-blind, placebo-controlled clinical study, 493 patients 18-80 years old with inadequate glycemic control after stabilization (i.e., glycosylated hemoglobin [HbA(1c)] 7.0-10.0%) despite ongoing treatment with a TZD were randomly assigned (2:2:1) to treatment with pioglitazone plus alogliptin 12.5 mg, alogliptin 25 mg or placebo once daily. Concomitant therapy with metformin or sulfonylurea at prestudy doses was permitted.
The primary efficacy endpoint was change in HbA(1c) from baseline to Week 26. Secondary endpoints included changes in fasting plasma glucose (FPG) and body weight, and incidences of marked hyperglycemia (FPG > or = 200 mg/dL [11.10 mmol/L]) and rescue for hyperglycemia.
Least squares (LS) mean change in HbA(1c) was significantly (p < 0.001) greater for alogliptin 12.5 mg (-0.66%) or 25 mg (-0.80%) than for placebo (-0.19%). A significantly (p < or = 0.016) larger proportion of patients achieved HbA(1c) < or = 7% with alogliptin 12.5 mg (44.2%) or 25 mg (49.2%) than with placebo (34.0%). LS mean decreases in FPG were significantly (p = 0.003) greater with alogliptin 12.5 mg (-19.7 mg/dL [-1.09 mmol/L]) or 25 mg (-19.9 mg/dL [-1.10 mmol/L]) than with placebo (-5.7 mg/dL [-0.32 mmol/L]). The percentage of patients with marked hyperglycemia was significantly (p < 0.001) lower for alogliptin (< or =25.0%) than placebo (44.3%). The incidences of overall adverse events and hypoglycemia were similar across treatment groups, but cardiac events occurred more often with active treatment than placebo.
Addition of alogliptin to pioglitazone therapy significantly improved glycemic control in patients with type 2 diabetes and was generally well tolerated. The study did not evaluate the effect of combination therapy on long-term clinical outcomes and safety.
NCT00286494, clinicaltrials.gov.
评估阿格列汀对使用噻唑烷二酮类药物（TZD）治疗血糖控制不佳的2型糖尿病患者的疗效及安全性。
在一项多中心、双盲、安慰剂对照的临床研究中，493例年龄在18 - 80岁、接受TZD治疗后血糖仍未得到有效控制（即糖化血红蛋白[HbA(1c)] 7.0 - 10.0%）的患者被随机分配（2:2:1），分别接受吡格列酮加12.5 mg阿格列汀、25 mg阿格列汀或安慰剂治疗，每日一次。允许患者继续使用研究前剂量的二甲双胍或磺脲类药物进行联合治疗。
主要疗效终点为从基线至第26周时HbA(1c)的变化。次要终点包括空腹血糖（FPG）和体重的变化，以及严重高血糖（FPG≥200 mg/dL [11.10 mmol/L]）的发生率和高血糖急救情况。
阿格列汀12.5 mg组（-0.66%）或25 mg组（-0.80%）的HbA(1c)最小二乘（LS）均值变化显著大于安慰剂组（-0.19%）（p < 0.001）。与安慰剂组（34.0%）相比，阿格列汀12.5 mg组（44.2%）或25 mg组（49.2%）达到HbA(1c)≤7%的患者比例显著更高（p≤0.016）。阿格列汀12.5 mg组（-19.7 mg/dL [-1.09 mmol/L]）或25 mg组（-19.9 mg/dL [-1.10 mmol/L]）的FPG LS均值下降幅度显著大于安慰剂组（-5.7 mg/dL [-0.32 mmol/L]）（p = 0.003）。阿格列汀组（≤25.0%）严重高血糖患者的比例显著低于安慰剂组（44.3%）（p < 0.001）。各治疗组总体不良事件和低血糖的发生率相似，但与安慰剂相比，活性治疗组心脏事件的发生率更高。
在吡格列酮治疗基础上加用阿格列汀可显著改善2型糖尿病患者的血糖控制，且总体耐受性良好。本研究未评估联合治疗对长期临床结局和安全性的影响。
NCT00286494，clinicaltrials.gov。
