利拉鲁肽与格列美脲联合二甲双胍对2型糖尿病的疗效和安全性比较

Comparison of efficacy and safety of liraglutide and glimepiride in combination with metformin in type 2 diabetes

目的观察中国2型糖尿病患者应用利拉鲁肽联合二甲双胍的疗效和安全性。方法本研究是一项2008年2月至2009年1月进行的为期16周的随机、双盲、双模拟临床试验，476例受试者被随机分为4组：利拉鲁肽（0．6、1．2或1．8mg，每日1次）联用二甲双胍、格列美脲（4mg，每日1次）联用二甲双胍（1g，每日2次）。主要疗效指标为糖化血红蛋白（HbAlC）的改变，次要疗效指标包括体质量、空腹血糖、7时点白测血糖谱、血压和p细胞功能等。各组疗效指标比较采用协方差模型进行分析。结果共476例受试者入组，其中男246例、女230例，平均年龄（54±9）岁，平均HbAlC8．3％±1．1％，平均体质指数（25±3）kg／m2，平均糖尿病病程6．9年。与基线相比，治疗后利拉鲁肽各治疗组HbAlC下降1．1％～1．2％，格列美脲组下降1．3％。利拉鲁肽1．2mg和1．8mg组中HbAlc的降低均非劣效于格列美脲组（95％C1分别为-0．15～0．31和-0．13～0．33，均P〈0．01）。治疗后利拉鲁肽各组体质量和收缩压的改变均显著优于格列美脲组：利拉鲁肽组体质量下降1．1～1．8kg，收缩压下降1．8～2．6mmHg（1mmHg=0．133kPa）；格列美脲组体质量增加0．6kg，收缩压升高2．1mmHg（均P〈0．05）。各利拉鲁肽组低血糖事件发生率均显著低于格列美脲组（分别为0．03、0、0．10和1．47次／人年，均P〈0．01）。结论利拉鲁肽在中国2型糖尿病患者中的整体耐受性良好，其降糖作用与格列美脲相当，并具有降低收缩压、减轻体质量和减少低血糖发生率的优势。

Objective To investigate the efficacy and safety of liraglutide added to metformin in Chinese patients with type 2 diabetes mellitus. Methods This 16-week, randomized, double-blind, double-dummy trial was eonducted from February 2008 to January 2009. The 476 subjects were randomized to receive either liraglutide （ 0. 6, 1.2 or 1.8 mg once daily ） or glimepiride （ 4 mg once daily ） , both combined with metformin （1 g twice daily）. The primary endpoint was change in HbAlc. The secondary endpoints included body weight, fasting blood glucose, systolic blood pressure （SBP） , etc . The efficacy endpoints were analysed by using analysis of covariance model. Results A total of 476 subjects （246 males and 230 females） with a mean age of （54 ±9） years, a mean HbAlc of 8.3% ± 1.1% , a mean body mass index（BMI） of （25 ± 3） kg/m2 and a mean duration of diabetes of 6. 9 years, were included in this trial.The demographic and clinical data were comparable among the treatment groups. Substantial reductions in HbAlc from baseline were observed for both liraglutide （ 1.1% - 1.2% ） and glimepiride （ I. 3% ） group. Both liraglutide 1.2 and 1.8 mg treatments was non-inferior to glimepiride in term of HbAlc reduction （95% CI： -0. 15 -0. 31, P 〈0. 01 ; 95% CI： -0. 13 -0. 33, P 〈0. 01, respectively）. Liraglutide led to significantly greater reduction in body weight （ 1.1 - 1.8 kg） and SBP （ 1.8 - 2. 6 mm Hg, 1 mm Hg = 0. 133 kPa） compared to glimepiride group （with an increase of O. 6 kg in body weight and 2. 1 mm Hg in SBP, all P 〈 O. 05）. All the liraglutide treatment groups showed lower risk of hypoglycemia in comparison with glimepiride group （ O. 03, 0, 0. 10 and 1.47 times/person-year, respectively; all P 〈 0. O1 ） . Conclusion Liraglutide is well tolerated and brings similar improvements in glycemic control with glimepiride and with additional benefits in body weight loss and SBP reduction and a lower risk of hypoglycemia in Chinese subjects with type 2 diabetes.