Terra S G, Somayaji V, Schwartz S, Lewin A J, Teeter J G, Dai H, Nguyen T T, Calle R A
Pfizer Global Research and Development, New London, Connecticut, USA.
Exp Clin Endocrinol Diabetes. 2011 Jul;119(7):401-7. doi: 10.1055/s-0031-1273737. Epub 2011 Apr 6.
The purpose of this phase 2, multicentre, randomized, double-blind, placebo-controlled, 12-week dose-ranging study was to assess the efficacy, safety, and tolerability of the dipeptidyl peptidase-IV (DPP-IV) inhibitor PF-734200 in adult subjects with type 2 diabetes who were on a stable dose of metformin. Men and women with inadequate glycaemic control with metformin as their sole diabetes medication were randomized to placebo or PF-734200 2 mg, 5 mg, 10 mg, or 20 mg every day. A population subset underwent mixed meal tolerance tests (MMTT) at baseline and week 12. A total of 301 subjects were treated. At week 12, PF-734200 doses of ≥5 mg produced a statistically significant reduction in haemoglobin A (1C) (HbA (1c)) compared with placebo. The mean (95% confidence interval) placebo-adjusted changes in HbA (1c) were -0.31% (-0.70 to 0.08), -0.74% (-1.12 to -0.36), -0.70% (-1.02 to -0.38), and -0.75% (-1.07 to -0.43) for the 2 mg, 5 mg, 10 mg, and 20 mg doses, respectively. PF-734200 20 mg significantly reduced glucose area under the curve following MMTT (-12.8% [-22.9 to -2.7]; p=0.003) compared with placebo. The reductions observed with other doses were not statistically significant. PF-734200 was safe and well tolerated at all doses tested when added to metformin. PF-734200 safely and effectively lowered HbA (1c) in subjects receiving metformin. The 20 mg dose provided the greatest improvements in post-prandial glucose.
这项2期、多中心、随机、双盲、安慰剂对照、为期12周的剂量范围研究的目的是评估二肽基肽酶-IV（DPP-IV）抑制剂PF-734200对正在接受稳定剂量二甲双胍治疗的2型糖尿病成年患者的疗效、安全性和耐受性。以二甲双胍作为唯一糖尿病药物但血糖控制不佳的男性和女性被随机分为安慰剂组或每天服用2毫克、5毫克、10毫克或20毫克PF-734200组。一个人群亚组在基线和第12周时进行了混合餐耐量试验（MMTT）。共有301名受试者接受了治疗。在第12周时，与安慰剂相比，PF-734200剂量≥5毫克可使糖化血红蛋白（HbA1c）出现具有统计学意义的降低。2毫克、5毫克、10毫克和20毫克剂量组的HbA1c平均（95%置信区间）安慰剂校正变化分别为-0.31%（-0.70至0.08）、-0.74%（-1.12至-0.36）、-0.70%（-1.02至-0.38）和-0.75%（-1.07至-0.43）。与安慰剂相比，PF-734200 20毫克显著降低了MMTT后的葡萄糖曲线下面积（-12.8%[-22.9至-2.7]；p=0.003）。其他剂量观察到的降低无统计学意义。当添加到二甲双胍中时，PF-734200在所有测试剂量下均安全且耐受性良好。PF-734200在接受二甲双胍治疗的受试者中安全有效地降低了HbA1c。20毫克剂量在餐后血糖方面提供了最大改善。
