贝那鲁肽每日2次注射治疗中国肥胖症患者的前瞻性多中心临床研究

A prospective multicenter clinical study of twice-daily injection of beinaglutide in the treatment of obese patients in China

目的探讨贝那鲁肽每日2次注射治疗中国肥胖症患者的疗效及安全性。方法为前瞻性多中心前后对照开放性非随机对照研究。选取2017年10月至2018年10月苏州大学附属第二医院内分泌科、南京医科大学附属逸夫医院内分泌科、常州市第一人民医院内分泌科、无锡市人民医院内分泌科、太仓市第一人民医院内分泌科的肥胖患者为研究对象。患者入组后先接受为期28 d的饮食控制和运动指导,继而以贝那鲁肽0.2 mg每日2次皮下注射治疗12周,监测患者体重及相关代谢指标。主要观察终点是贝那鲁肽治疗前后的体重变化,次要终点是贝那鲁肽治疗前后的代谢或心血管相关风险因素(血压、腰围、臀围)的变化,同时收集糖耐量异常患者恢复到正常的比例。采用配对t检验比较治疗前后患者相关指标的差异。结果共91例肥胖症患者纳入研究,其中最后有70.3%(64/91)的患者完成试验。与治疗前相比,应用贝那鲁肽每日2次注射治疗12周后64例患者体重下降[分别为(93.15±15.39)kg和(89.30±14.52)kg,t=-9.03,P<0.001]。有31.9%(29/91)的患者体重下降≥5%,6.6%(6/91)的患者体重下降≥10%。与治疗前相比,治疗12周后,患者腰围[分别为(104.22±11.20)cm和(99.80±9.66)cm,t=-7.12,P<0.001]、臀围[分别为(110.80±8.43)cm和(107.10±7.89)cm,t=-6.39,P<0.001]、收缩压[分别为(129.66±14.89)mmHg和(125.60±11.39)mmHg,t=-2.96,P=0.004]均下降。入组时有36.3%(33/91)的患者存在糖耐量异常,干预治疗12周后有24.2%(8/33)的患者恢复正常。在此次研究中不良反应主要为恶心、呕吐和食欲减退,未发现严重不良事件。结论每日2次给予贝那鲁肽皮下注射联合饮食和运动干预对中国肥胖患者进行综合治疗,有减重及改善代谢或心血管相关风险因素的疗效,且安全性和耐受性良好。

Objective To explore the efficacy and safety of beinaglutide injection twice daily in the treatment of Chinese patients with obesity.Methods A prospective,multicenter,open-label,before and after controlled study was conducted.From October 2017 to October 2018,obese patients in Department of Endocrinology of the Second Affiliated Hospital of Soochow University,Department of Endocrinology of Yifu Hospital Affiliated to Nanjing Medical University,Department of Endocrinology of Changzhou First People′s Hospital,Department of Endocrinology of Wuxi People′s Hospital,Department of Endocrinology of Taicang First People′s Hospital were selected as the research subjects.After enrolment,patients received 28 days of dietary control and exercise guidance,followed by 12 weeks of treatment with subcutaneous injections of beinaglutide 0.2 mg Bid,during which time patients′weight and other metabolic indicators were monitored.The primary endpoint was the change in weight before and after beinaglutide treatment,and the secondary endpoint was the change in metabolic or cardiovascular risk factors(blood pressure,waist circumference,hip circumference)before and after beinaglutide treatment,as well as the proportion of patients with impaired glucose tolerance who returned to normal.Paired t test was used to compare the differences in the relevant indicators before and after treatment.Results A total of 91 obese patients from 5 hospitals were enrolled in this study,and 64 patients(70.3%)completed the trial.After 12 weeks of treatment,the patients′weight decreased from(93.15±15.39)kg at baseline to(89.30±14.52)kg(t=-9.03,P<0.001).31.9%(29/91)of the subjects had a weight loss of≥5%,and 6.6%(6/91)had a weight loss of≥10%.After 12 weeks of treatment,the patients′waist circumference decreased from(104.22±11.20)cm at baseline to(99.80±9.66)cm(t=-7.12,P<0.001),and hip circumference decreased from(110.80±8.432)cm at baseline to(107.10±7.89)cm(t=-6.39,P<0.001),and systolic blood pressure decreased from(129.66±14.89)mmHg at baseline to(125.60±11.39)mmHg(t=-2.96,P=0.004).At baseline,36.3%(33/91)had impaired glucose tolerance,and at the 12-week follow-up,24.2%(8/33)patients had returned to normal.In this study,the most common adverse reactions were nausea,vomiting and loss of appetite,with no serious adverse events were reported.Conclusion The twice-daily subcutaneous injection of beinaglutide combined with diet and exercise intervention for the comprehensive treatment of Chinese patients with simple obesity and combined metabolic abnormalities has therapeutic effects on weight loss and improvement of metabolic or cardiovascular-related risk factors,with good safety and tolerability.