Horton E S, Clinkingbeard C, Gatlin M, Foley J, Mallows S, Shen S
Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
Diabetes Care. 2000 Nov;23(11):1660-5. doi: 10.2337/diacare.23.11.1660.
To evaluate the efficacy and tolerability of nateglinide and metformin alone and in combination in type 2 diabetic patients inadequately controlled by diet, focusing on changes in HbA1c, fasting plasma glucose (FPG), and mealtime glucose excursions.
In this randomized double-blind study, patients with an HbA1c level between 6.8 and 11.0% during a 4-week placebo run-in received 24 weeks' treatment with 120 mg nateglinide before meals (n = 179), 500 mg metformin three times a day (n = 178), combination therapy (n = 172), or placebo (n = 172). HbA1c and FPG were evaluated regularly, and plasma glucose levels were determined after Sustacal challenge at weeks 0, 12, and 24. Hypoglycemia and other adverse events were recorded.
At study end point, HbA1c was reduced from baseline with nateglinide and metformin but was increased with placebo (-0.5, -0.8, and +0.5%, respectively; P < or = 0.0001). Changes in FPG followed the same pattern (-0.7, -1.6, and +0.4 mmol/l; P < or = 0.0001). Combination therapy was additive (HbA1c -1.4% and FPG -2.4 mmol/l; P < or = 0.01 vs. monotherapy). After Sustacal challenge, there was a greater reduction in mealtime glucose with nateglinide monotherapy compared with metformin monotherapy or placebo (adjusted area under the curve [AUC]0-130 min -2.1, -1.1, and -0.6 mmol x h(-1) x l(-1); p < or = 0.0001). An even greater effect was observed with combination therapy (AUC0-130 min -2.5 mmol x h(-1) x l(-1); P < or = 0.0001 vs. metformin and placebo). All regimens were well tolerated.
Nateglinide and metformin monotherapy each improved overall glycemic control but by different mechanisms. Nateglinide decreased mealtime glucose excursions, whereas metformin primarily affected FPG. In combination, nateglinide and metformin had complementary effects, improving HbA1c, FPG, and postprandial hyperglycemia.
评估那格列奈和二甲双胍单药及联合用药对饮食控制不佳的2型糖尿病患者的疗效和耐受性，重点关注糖化血红蛋白（HbA1c）、空腹血糖（FPG）及进餐期间血糖波动的变化。
在这项随机双盲研究中，糖化血红蛋白水平在4周安慰剂导入期为6.8%至11.0%的患者接受24周治疗，分别为饭前服用120mg那格列奈（n = 179）、每日三次服用500mg二甲双胍（n = 178）、联合治疗（n = 172）或安慰剂（n = 172）。定期评估糖化血红蛋白和空腹血糖，并在第0、12和24周进行Sustacal激发试验后测定血糖水平。记录低血糖及其他不良事件。
在研究终点，那格列奈和二甲双胍治疗组的糖化血红蛋白较基线水平降低，而安慰剂组升高（分别为-0.5%、-0.8%和+0.5%；P≤0.0001）。空腹血糖变化呈现相同模式（分别为-0.7、-1.6和+0.4mmol/l；P≤0.0001）。联合治疗具有相加作用（糖化血红蛋白-1.4%，空腹血糖-2.4mmol/l；与单药治疗相比，P≤0.01）。在Sustacal激发试验后，与二甲双胍单药治疗或安慰剂相比，那格列奈单药治疗对进餐期间血糖的降低作用更大（曲线下面积[AUC]0-130分钟调整后分别为-2.1、-1.1和-0.6mmol·h-1·l-1；P≤0.0001）。联合治疗效果更显著（AUC0-130分钟为-2.5mmol·h-1·l-1；与二甲双胍和安慰剂相比，P≤0.0001）。所有治疗方案耐受性良好。
那格列奈和二甲双胍单药治疗均能改善总体血糖控制，但机制不同。那格列奈降低进餐期间血糖波动，而二甲双胍主要影响空腹血糖。联合使用时，那格列奈和二甲双胍具有互补作用，可改善糖化血红蛋白、空腹血糖及餐后高血糖。
