Rosenstock J, Rood J, Cobitz A, Huang C, Garber A
Dallas Diabetes and Endocrine Center, Dallas, TX 75230, USA.
Diabetes Obes Metab. 2006 Nov;8(6):643-9. doi: 10.1111/j.1463-1326.2006.00648.x.
Traditional first-line intervention in patients with type 2 diabetes and very poor glycaemic control is insulin therapy or high doses of sulfonylureas if there is no evidence of volume depletion. This study explored the safety and efficacy of open-label treatment with rosiglitazone and metformin (RSG/MET) fixed-dose combination therapy (AVANDAMET) in patients with type 2 diabetes with very poor glycaemic control, to better characterize the magnitude of glycated haemoglobin (A1c) reduction after 24 weeks of therapy.
In this multicentre, open-label trial, 190 patients with an A1c greater than 11% or fasting plasma glucose (FPG) greater than 15 mmol/l were included after failing to meet glycaemic entry criteria for a primary double-blind, controlled, randomized study. Unless tolerability issues arose, eligible patients initiated RSG/MET 4 mg/1000 mg fixed-dose combination therapy and were up-titrated in increments of 2 mg/500 mg at 4-week intervals to a daily dose of 8 mg/2000 mg or the maximum tolerated dose. Patients were assessed for efficacy and safety at five visits over a 24-week period. The primary efficacy end point was change from baseline in A1c at week 24. Secondary efficacy end points included the proportion of patients achieving defined A1c targets, change from baseline to week 24 in FPG and insulin sensitivity.
The majority of patients (78%) completed 24 weeks of open-label treatment. At week 24, clinically significant mean reduction in A1c from 11.8 to 7.8% (mean reduction, 4.0 +/- 2.2%; p < 0.0001) and mean FPG reduction from 16.9 to 9.2 mmol/l (mean reduction, 7.7 +/- 4.4 mmol/l; p < 0.0001) were observed. A clinically significant reduction in FPG (5.2 mmol/l) was observed after 4 weeks of treatment with RSG/MET fixed-dose combination therapy. Despite a high mean baseline A1c of 11.8%, 33% of patients achieved treatment goal of A1c less than or equal to 6.5% at week 24, and 44% achieved an A1c less than 7% at week 24. RSG/MET fixed-dose combination was well tolerated, with a low incidence of hypoglycaemia (2%) and mean increase in weight from baseline of 2.6 +/- 5.2 kg, and few patients withdrew (2.6%) because of an adverse event.
RSG/MET fixed-dose combination therapy was effective as initial therapy in patients with type 2 diabetes and very high levels of A1c and/or FPG, as demonstrated by robust and relatively rapid improvements in glycaemic control. RSG/MET fixed-dose combination was well tolerated as first-line therapy with no new tolerability issues identified.
对于2型糖尿病且血糖控制极差的患者，传统的一线干预措施是胰岛素治疗，或者在无容量耗竭证据时使用高剂量磺脲类药物。本研究探讨了罗格列酮与二甲双胍（RSG/MET）固定剂量复方疗法（AVANDAMET）开放标签治疗2型糖尿病且血糖控制极差患者的安全性和有效性，以更好地描述治疗24周后糖化血红蛋白（A1c）降低的幅度。
在这项多中心、开放标签试验中，190例A1c大于11%或空腹血糖（FPG）大于15 mmol/L的患者在未达到一项主要双盲、对照、随机研究的血糖纳入标准后被纳入。除非出现耐受性问题，符合条件的患者开始使用4 mg/1000 mg的RSG/MET固定剂量复方疗法，并以2 mg/500 mg的增量每4周上调一次剂量，直至每日剂量达到8 mg/2000 mg或最大耐受剂量。在24周期间的五次访视中对患者进行疗效和安全性评估。主要疗效终点是第24周时A1c相对于基线的变化。次要疗效终点包括达到既定A1c目标的患者比例、从基线到第24周FPG的变化以及胰岛素敏感性。
大多数患者（78%）完成了24周的开放标签治疗。在第24周时，观察到A1c从11.8%降至7.8%有临床显著意义的平均降低（平均降低4.0 +/- 2.2%；p < 0.0001），FPG从16.9 mmol/L降至9.2 mmol/L有临床显著意义的平均降低（平均降低7.7 +/- 4.4 mmol/L；p < 0.0001）。使用RSG/MET固定剂量复方疗法治疗4周后观察到FPG有临床显著降低（5.2 mmol/L）。尽管平均基线A1c高达11.8%，但在第24周时33%的患者达到了A1c小于或等于6.5%的治疗目标，44%的患者在第24周时A1c小于7%。RSG/MET固定剂量复方耐受性良好，低血糖发生率低（2%），体重相对于基线平均增加2.6 +/- 5.2 kg，很少有患者（2.6%）因不良事件退出。
RSG/MET固定剂量复方疗法作为2型糖尿病且A1c和/或FPG水平极高患者的初始治疗有效，血糖控制得到有力且相对快速的改善证明了这一点。RSG/MET固定剂量复方作为一线治疗耐受性良好，未发现新的耐受性问题。
