Wolffenbuttel B H, Gomis R, Squatrito S, Jones N P, Patwardhan R N
University Hospital Maastricht, The Netherlands.
Diabet Med. 2000 Jan;17(1):40-7. doi: 10.1046/j.1464-5491.2000.00224.x.
This study was designed to test the efficacy and safety of low-dose rosiglitazone, a potent, insulin-sensitizing thiazolidinedione, in combination with sulphonylurea in Type 2 diabetic patients.
For the intention-to-treat analysis, 574 patients (59% male, mean age 61 years) were available, randomized to receive 26 weeks of twice-daily placebo (n = 192), rosiglitazone 1 mg (n = 199) or rosiglitazone 2 mg (n = 183) in addition to existing sulphonylurea treatment with gliclazide (47.6% of patients), glibenclamide (41.8%) or glipizide (9.4%) (two patients were taking carbutamide or glimepiride). Change in haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fructosamine, insulin, C-peptide, albumin, and lipids were measured, and safety was evaluated.
Mean baseline HbA1c was 9.2% and FPG was 11.4 mmol/l. Rosiglitazone at doses of 1 and 2 mg b.d. plus sulphonylurea produced significant decreases, compared with sulphonylurea plus placebo, in HbA1c (-0.59% and -1.03%, respectively; both P<0.0001) and FPG (1.35 mmol/l and 2.44 mmol/l, respectively; both P<0.0001). Both HDL-cholesterol and LDL-cholesterol increased and potentially beneficial decreases in non-esterified fatty acids and gamma glutamyl transpeptidase levels were seen in both rosiglitazone groups. The overall incidence of adverse experiences was similar in all three treatment groups, with no significant cardiac events, hypoglycaemia or hepatotoxicity.
Overall, the combination of rosiglitazone and a sulphonylurea was safe, well tolerated and effective in patients with Type 2 diabetes.
本研究旨在测试低剂量罗格列酮（一种强效的胰岛素增敏噻唑烷二酮类药物）与磺脲类药物联合使用治疗2型糖尿病患者的疗效和安全性。
在意向性分析中，共有574例患者（男性占59%，平均年龄61岁），随机接受为期26周的每日两次安慰剂治疗（n = 192）、罗格列酮1毫克（n = 199）或罗格列酮2毫克（n = 183），这些治疗均在已有的磺脲类药物（格列齐特治疗的患者占47.6%，格列本脲占41.8%，格列吡嗪占9.4%）（两名患者服用的是卡比马脲或格列美脲）治疗基础上进行。测量糖化血红蛋白（HbA1c）、空腹血糖（FPG）、果糖胺、胰岛素、C肽、白蛋白和血脂的变化，并评估安全性。
平均基线糖化血红蛋白为9.2%，空腹血糖为11.4毫摩尔/升。与磺脲类药物加安慰剂相比，每日两次服用1毫克和2毫克罗格列酮加磺脲类药物可使糖化血红蛋白（分别降低-0.59%和-1.03%；P均<0.0001）和空腹血糖（分别降低1.35毫摩尔/升和2.44毫摩尔/升；P均<0.0001）显著降低。两个罗格列酮组的高密度脂蛋白胆固醇和低密度脂蛋白胆固醇均升高，且非酯化脂肪酸和γ-谷氨酰转肽酶水平出现了潜在的有益下降。所有三个治疗组的不良事件总发生率相似，未发生明显的心脏事件、低血糖或肝毒性。
总体而言，罗格列酮与磺脲类药物联合使用对2型糖尿病患者是安全、耐受性良好且有效的。
