Two-year efficacy and safety of initial combination therapy with nateglinide or glyburide plus metformin
Two-year efficacy and safety of initial combination therapy with nateglinide or glyburide plus metformin
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DOI：
10.2337/diacare.28.9.2093
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发表时间：
2005-09-01
期刊：
影响因子：
16.2
通讯作者：
Baron, MA
中科院分区：
文献类型：
--
作者：
Gerich, J;Raskin, P;Baron, MA
目的-比较那格列奈/二甲双胍与格列本脲/二甲双胍初始联合治疗的长期疗效和安全性。研究设计与方法-我们对428名未服药的2型糖尿病患者进行了一项随机、多中心、双盲、为期2年的研究。患者接受120毫克交流。那格列奈或1.25 mg q.d。格列本脲加500 mg qd。开放标签的二甲双胍，最初4周。在随后的12周滴定期间，格列本脲和二甲双胍分别增加1.25和500毫克，达到每日最大剂量，分别为10毫克和2,000毫克，如果两周的空腹血糖=6.7 mmol/L。那格列奈没有被滴定。通过使用那格列奈和格列本脲相匹配的安慰剂来维持失明。结果：那格列奈/二甲双胍治疗的患者糖化血红蛋白在基线时为8.4%，第104周时为6.9%。在格列本脲/二甲双胍治疗的患者中，平均糖化血红蛋白在基线时为8.3%，在第104周时为6.8%(P<；两种治疗方法与基线相比P<；0.0001，两种治疗方法之间为NS)。DeltaPPGE平均值为-96+/-19(P<；0.0001)和-57+/-22 mmo1(-1)(.)在那格列奈/二甲双胍和格列本脲/二甲双胍治疗的患者中，每分钟血糖分别为-1.6+/-0.2(P<；0.0001)和-2.4+/-0.2 mm ol/L(P<；0.0001)。因此，两种治疗方法取得了相似的疗效，但对FPG和PPGE的影响不同。接受那格列奈/二甲双胍和格列本脲/二甲双胍治疗的患者中，分别有8.2%和17.7%的患者出现低血糖。结论：无论哪种治疗方案，都可以将相似的良好血糖控制维持2年，但那格列奈/二甲双胍可能是一种更安全的初始联合治疗方法。
OBJECTIVE - To compare long-term efficacy and safety of initial combination therapy with nateglinide/metformin versus glyburide/metformin.RESEARCH DESIGN AND METHODS- We conducted a randomized, multicenter, double-masked, 2-year study of 428 drug-naive patients with type 2 diabetes. Patients received 120 mg a.c. nateglinide or 1.25 mg q.d. glyburide plus 500 mg q.d. open-label metformin for the initial 4 weeks. During a subsequent 12-week titration period, glyburide and metformin were increased by 1.25- and 500-mg increments to maximum daily doses of 10 and 2,000 mg, respectively, if biweekly fasting plasma glucose (FPG) >= 6.7 mmol/l. Nateglinide was not titrated. Blinding was maintained by use of matching placebo for nateglinide and glyburide. An 88-week monitoring period followed, during which HbA(Ic) (AlC), FPG, and postprandial glucose excursions (PPGEs) during an oral glucose tolerance test were measured.RESULTS- In nateglinide/metformin-treated patients, mean AlC was 8.4% at baseline and 6.9% at week 104. In glyburide/metformin-treated patients, mean AlC was 8.3% at baseline and 6.8% at week 104 (P < 0.0001 vs. baseline for both treatments, NS between treatments). The Delta PPGE averaged -96 +/- 19 (P < 0.0001) and -57 +/- 22 mmol (.)1(-1) (.) min(-1) (P < 0.05) in patients receiving nateglinide/metformin and glyburide/metformin, respectively, whereas Delta FPG was -1.6 +/- 0.2 (P < 0.0001) and -2.4 +/- 0.2 mmol/l (P < 0.0001) in patients receiving nateglinide/metformin and glyburide/metformin, respectively (P < 0.01 between groups). Thus, the two treatments achieved similar efficacy with differential effects on FPG versus PPGE. Hypoglycemia occurred in 8.2 and 17.7% of patients receiving nateglinide/metformin and glyburide/metformin, respectively.CONCLUSIONS - Similar good glycemic control can be maintained for 2 years with either treatment regimen, but nateglinide/metformin may represent a safer approach to initial combination therapy.