Barnett A H, Anderson D M, Shelley S, Morgan R, Owens D R
Department of Medicine, Birmingham Heartlands Hospital, University of Birmingham, Birmingham, UK.
Diabetes Obes Metab. 2004 Mar;6(2):104-13. doi: 10.1111/j.1462-8902.2004.00321.x.
This was a randomized, double blind, three period crossover study. The objective was to compare glucose, insulin and C-peptide 24 h profiles in patients with type 2 diabetes mellitus after dosing with nateglinide (given preprandially before three test meals), glibenclamide (administered once before breakfast) or placebo (given before three test meals).
Fourteen patients underwent screening followed within 3 weeks by three treatment periods of 1 day, each separated by 7 days. Dosing followed a six-sequence balanced, two 3 x 3-replicated Latin square.
Mean peak serum insulin levels were lower after nateglinide (115 mU/l) than after glibenclamide (145 mU/l.h; p = 0.017) but higher than after placebo (79 mU/l; p = 0.001). However, peak insulin levels were reached earlier after nateglinide [mean time to peak (tmax) 1.7 h] compared to glibenclamide (mean tmax 2.1 h, p = 0.06). Total insulin exposure over the day was higher after glibenclamide compared with that following nateglinide (1216 vs. 1067 mU/l.h; p = 0.009). Similar findings were seen with serum C-peptide. Despite this, mean peak plasma glucose concentrations were lower following nateglinide (11.4 mmol/l from a baseline of 8.3 mmol/l) compared with glibenclamide (13.2 mmol/l from a baseline of 8.5 mmol/l; p = 0.001) and placebo (14.0 mmol/l from a baseline of 8.0 mmol/L; p < 0.001).
Nateglinide improves early prandial measures of insulin and glucose response to a standard meal, more so than glibenclamide, in people with type 2 diabetes.
这是一项随机、双盲、三阶段交叉研究。目的是比较2型糖尿病患者在服用那格列奈（在三次试验餐餐前给药）、格列本脲（早餐前一次给药）或安慰剂（在三次试验餐餐前给药）后24小时的血糖、胰岛素和C肽水平变化情况。
14名患者接受筛选，在3周内进行三个为期1天的治疗阶段，每个阶段间隔7天。给药遵循六序列平衡、两个3×3重复拉丁方设计。
那格列奈给药后血清胰岛素平均峰值水平（115 mU/l）低于格列本脲给药后（145 mU/l.h；p = 0.017），但高于安慰剂给药后（79 mU/l；p = 0.001）。然而，那格列奈达到胰岛素峰值水平的时间更早[平均达峰时间（tmax）1.7小时]，相比之下格列本脲的平均达峰时间为2.1小时（p = 0.06）。与那格列奈相比，格列本脲给药后全天的胰岛素总暴露量更高（1216对1067 mU/l.h；p = 0.009）。血清C肽也有类似发现。尽管如此，那格列奈给药后平均血浆葡萄糖峰值浓度（从基线8.3 mmol/l升至11.4 mmol/l）低于格列本脲（从基线8.5 mmol/l升至13.2 mmol/l；p = 0.001）和安慰剂（从基线8.0 mmol/L升至14.0 mmol/l；p < 0.001）。
对于2型糖尿病患者，那格列奈比格列本脲更能改善对标准餐的胰岛素和血糖早期餐时反应指标。
