二甲双胍与格列喹酮或阿卡波糖联合治疗2型糖尿病的临床疗效和安全性比较:多中心、随机、开放、平行分组对照研究

Efficacy and tolerability of sustained-release metformin in combination with gliquidone or acarbose for the treatment of type 2 diabetes mellitus:a multicentre, randomized, open-labeled and parallelgroup study

目的 对用单药和(或)联合口服降糖药物后血糖控制不佳的2型糖尿病患者,比较二甲双胍缓释片分别联合格列喹酮或阿卡波糖治疗的疗效和安全性.方法 选取符合研究方案的2型糖尿病患者140例,男74例,女66例,平均年龄(56±10)岁,随机分为二甲双胍(1500 mg/d)+格列喹酮(初始剂量为30 mg,2次/d)组70例和二甲双胍(1500 mg/d)+阿卡波糖(初始剂量为50mg,2次/d)组70例,维持治疗14周.在基线和治疗结束时分别进行各项生化指标和胰岛素反应等检查.以糖化血红蛋白(HbA1c)是否达标为因变量,调整年龄、性别、糖尿病病程、基线时β胰岛功能和体重指数、治疗分组后,进行Logistic多元逐步回归分析.结果 (1)经14周治疗后,两组HbA1c均较治疗前显著下降,格列喹酮组为(7.4±1.1)%,阿卡波糖组为(7.8±1.1)%,格列喹酮组下降幅度更大,平均HbA1c下降1.7%(t=-4.404,P=0.0001),差异有统计学意义.HbA1c<6.5%的达标率在格列喹酮组有高于阿卡波糖组趋势(25.71%比12.86%,χ2=3.72,P=0.054).(2)两组胰岛素抵抗指数均较各自治疗前显著下降,但两组间比较无显著差异.二甲双胍+格列喹酮组在治疗过程中无严重低血糖事件或其他严重不良事件发生,患者耐受件良好.结论 格列喹酮在单药和(或)联合治疗失败的2型糖尿病中与二甲双胍联合治疗能有效降低2型糖尿病患者血糖,在HbA1c达标率较高的同时安全性较好.

Objective To understand the efficacy and safety of sufficient dose of metformin either plus gliquidone or plus acarbose for the treatment of type 2 diabetes mellitus. Method One hundred and forty patients with type 2 diabetes who were inadequately controlled with previous therapy were randomized to receive sustained-release metformin (1500 mg/d) in combination with either gliquidone (start with 30 mg, bid) or acarbose(start with 50 mg,bid) for 14 weeks. The anthropometric parameters, fasting blood glucose levels, lipid profiles, HbA1c and post-challenge glucose and insulin responses were measured at baseline and at the end of treatment. Results After 14 weeks treatment, the level of the glycated hemoglobin A1c (HbA1c) in the 2 group were both decreased than before(metformin + gliquidoue group with (7.4±1.1)%, metformin + acarbose group with (7.8±1.1)%). The level of HbA1c decreased significantly more in metformin plus gliquidone group (1.7%) than in mefformin plus acarbose group (0.9%), P =0.0001. The rate of HbA1c <6.5% was 25.71% in mefformin plus gliquidone group, compared to 12.86% in mefformin plus acarbose group(P =0.054). The insulin resistance index(HOMA-IR) and the beta-cell function index (HOMA-β) improved significantly in both groups, but no difference was observed between the two groups. Conclusion As compared to mefformin plus acarbose, the combined therapy with mefformin plus gliquidone more significantly improved glycemic control and was well tolerated among inadequately controlled patients with type 2 diabetes.