Horton Edward S, Foley James E, Shen Sharon G, Baron Michelle A
Joslin Diabetes Center, Boston, Massachusetts, USA.
Curr Med Res Opin. 2004 Jun;20(6):883-9. doi: 10.1185/030079903125003881.
To assess the efficacy and tolerability of the combination of nateglinide (120 mg, ac) and metformin (500 mg, tid) as initial treatment in drug-naïve patients with type 2 diabetes mellitus (T2DM).
This study reports data from the treatment-naïve (TN) subgroup of patients in a previously published, randomized, multicenter, placebo-controlled, 24- week trial that compared nateglinide, metformin, and the combination therapy (CT) in 701 patients with T2DM with baseline HbA(1c) between 6.8% and 11.0%. Of the 401 TN patients, 104, 104, 89, and 104 patients received nateglinide (120 mg, ac), metformin (500 mg, tid), CT, and placebo, respectively. The baseline characteristics of each group were similar, with mean age, BMI, duration of diabetes, HbA(1c), and fasting plasma glucose (FPG) levels of approximately 58 years, 30 kg/m(2), 4 Gastrointestinal side effects occurred in 27% of years, 8.2%, and 10.2 mmol/L, respectively.
In patients receiving initial CT, HbA(1c) decreased substantially (Delta = -1.6 +/- 0.1%, p < 0.0001 vs. baseline or placebo) from a mean baseline of 8.2 +/- 0.1%, an effect significantly greater than the 0.8% reduction observed with both monotherapies (p < 0.001); whereas, in placebo-treated patients, HbA(1c) increased modestly (Delta = +0.3 +/- 0.1%, p < 0.05) from an identical baseline value. Seventy percent of CT-treated patients achieved a target HbA(1c) of < 7.0%. Both fasting plasma glucose (FPG) and the 2-hour postprandial glucose excursion (PPGE) after a liquid meal challenge decreased by 2.3 mmol/L in patients receiving CT, while the changes from baseline values in FPG and PPGE were +0.2 +/- 0.3 mmol/L and -0.5 +/- 0.2 mmol/L, respectively, in placebo-treated patients. The incremental 30-minute post-load insulin levels increased by 88 +/- 32 pmol/L (p = 0.006) in patients receiving CT and did not change significantly in placebo-treated patients. patients receiving CT (vs. 27.9% in the metformin monotherapy, and 14.4% in the placebo groups). Confirmed hypoglycemia (glucose <or= 2.8 mmol/L) occurred in 3.4% of patients receiving CT.
Initial CT with the rapid-acting insulinotropic agent, nateglinide, and metformin, an agent with insulin-sensitizing effects in the liver and periphery, is a safe and effective means of achieving glycemic targets in TN patients with T2DM.
评估那格列奈（120毫克，餐前）与二甲双胍（500毫克，每日三次）联合用药作为初治2型糖尿病（T2DM）患者初始治疗的疗效和耐受性。
本研究报告了一项先前发表的、随机、多中心、安慰剂对照、为期24周试验中初治（TN）亚组患者的数据，该试验比较了那格列奈、二甲双胍及联合治疗（CT）在701例基线糖化血红蛋白（HbA1c）在6.8%至11.0%之间的T2DM患者中的疗效。在401例TN患者中，分别有104例、104例、89例和104例患者接受那格列奈（120毫克，餐前）、二甲双胍（500毫克，每日三次）、联合治疗和安慰剂治疗。每组的基线特征相似，平均年龄、体重指数、糖尿病病程、HbA1c及空腹血糖（FPG）水平分别约为58岁、30千克/米²、4年、8.2%和10.2毫摩尔/升。
接受初始联合治疗的患者，HbA1c从平均基线值8.2±0.1%大幅下降（差值=-1.6±0.1%，与基线或安慰剂相比，p<0.0001），这一效果显著大于两种单一疗法所观察到的0.8%的降幅（p<0.001）；而在接受安慰剂治疗的患者中，HbA1c从相同的基线值略有上升（差值=+0.3±0.1%，p<0.05）。70%接受联合治疗的患者达到了HbA[1c]<7.0%的目标。接受联合治疗的患者，空腹血糖（FPG）及液体餐激发后2小时餐后血糖波动（PPGE）均下降了2.3毫摩尔/升，而接受安慰剂治疗的患者FPG和PPGE相对于基线值的变化分别为+0.2±0.3毫摩尔/升和-0.5±0.2毫摩尔/升。接受联合治疗的患者负荷后30分钟胰岛素水平增量增加了88±32皮摩尔/升（p=0.006），而接受安慰剂治疗的患者无显著变化。接受联合治疗的患者出现胃肠道副作用的比例为27%（二甲双胍单一疗法组为27.9%，安慰剂组为14.4%）。接受联合治疗的患者中确诊低血糖（血糖≤2.8毫摩尔/升）的发生率为3.4%。
初治T2DM患者采用速效促胰岛素分泌剂那格列奈与具有肝脏和外周胰岛素增敏作用的二甲双胍进行联合治疗，是实现血糖目标的一种安全有效的方法。
