长效GLP—1受体激动药索马鲁肽治疗2型糖尿病疗效和安全性的系统评价(1)
摘 要 目的：系統评价长效胰高血糖素样肽-1(GLP-1)受体激动药索马鲁肽对比安慰剂或其他降糖药治疗2型糖尿病的疗效和安全性，为临床治疗提供循证参考。方法：计算机检索PubMed、Embase、Medline、Cochrane图书馆，检索时限为自建库起至2018年9月，收集索马鲁肽(试验组)对比安慰剂或其他降糖药(对照组)治疗2型糖尿病疗效和安全性的随机对照试验(RCT)，对符合纳入标准的临床研究进行资料提取并采用Cochrane系统评价手册5.1.0进行质量评价后，使用Rev Man 5.3软件对治疗前后患者的糖化血红蛋白(HbA1c)水平及达标率、空腹血糖(FPG)水平、收缩压、舒张压、体质量指数(BMI)、体质量、脉搏频率水平、低血糖和胃肠道反应发生率等指标进行Meta分析。结果：共纳入12项RCT，合计9 966例患者。Meta分析结果显示，试验组相比于对照组能更有效降低HbA1c水平[MD=-1.03，95%CI(-1.22，-0.85)，P<0.001]和FPG水平[MD=-1.14，95%CI(-1.53，-0.76)，P<0.001]，增加受试患者HbA1c达标率[RD=0.40，95%CI(0.31，0.49)，P<0.001]，同时还可降低收缩压[MD=-2.61，95%CI (-3.23，-1.98)，P<0.001]、舒张压[MD=-0.56，95%CI(-0.96，-0.16)，P=0.006]、BMI[MD=-1.25，95%CI(-1.51， -0.99)，P<0.001]，减轻体质量[MD=-3.60 ，95%CI(-4.24，-2.96)，P<0.001]，增加脉搏频率[MD=2.16，95%CI(1.51，2.81)，P<0.001]，差异均有统计学意义；索马鲁肽的主要不良反应为胃肠道反应，其发生率高于对照组[RD=0.20，95%CI(0.15，0.26)，P<0.001]、低血糖事件的发生率与对照组比较，差异则无统计学意义 [RD=0.00，95%CI(-0.01，0.02)，P=0.44]。结论：索马鲁肽可明显降低2型糖尿病患者的HbA1c、FPG、体质量、血压水平，增加脉搏频率，提高服用患者的HbA1c达标率；同时，虽然其致胃肠道反应发生率高于对照组，但不会增加低血糖发生的风险，提示该药具有较好的耐受性和安全性。
关键词 胰高血糖素样肽-1受体激动药；索马鲁肽；2型糖尿病；有效性；安全性；系统评价
Efficacy and Safety of Long-acting GLP-1 Receptor Agonist Semaglutide for Type 2 Diabetes： A Systematic Review
LU Zhiwei1，SUN Hao2，LI Ying1，XIAO Longke1，DONG Yan1，LIU Aina1，ZHAO Zhenyu1(1.Dept. of Pharmacy， Research Institute of Endocrinology， Metabolic Diseases Hospital of Tianjin Medical University/Key Lab of Hormones and Development， Ministry of Public Health， Tianjin 300070， China；2.Dept. of Pharmacy， the Affiliated Hospital of Tianjin Institute for TCM， Tianjin 300020， China)
ABSTRACT OBJECTIVE： To systematically evaluate therapeutic efficacy and safety of long-acting glucagon like peptide-1 (GLP-1) receptor agonist Semaglutide vs. placebo or other glucose-lowering drugs in the treatment of type 2 diabetes mellitus (T2DM)， and to provide evidence-based reference for T2DM in clinic. METHODS： Retrieved from PubMed， Embase， Medline， Cochrane library， randomized controlled trials (RCT) about Semaglutide (trial group) vs. placebo or other glucose-lowering drugs (control group) in the treatment of T2DM were selected during the establishment of database to Sept. 2018. After data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0， Meta-analysis was performed for HbA1c level and compliance rate， fasting plasma glucose (FPG) level， systolic blood pressure (SBP)， diastolic blood pressure (DBP)， body mass index (BMI)， body weight pulse frequency level， the incidence of hypoglycemia and gastrointestinal reaction by using Rev Man 5.3 software. RESULTS： A total of 12 RCTs involving 9 966 patients were included. The results of Meta-analysis showed that compared with control group， trial group could effectively decrease the levels of HbA1c [MD=-1.03， 95%CI(-1.22，-0.85)， P<0.001] and FPG [MD=-1.14， 95%CI(-1.53，-0.76)， P<0.001]， increase compliance rate of HbA1c [RD=0.40， 95%CI(0.31，0.49)， P<0.001]， reduce SBP [MD=-2.61， 95%CI (-3.23， -1.98)， P<0.001] and DBP [MD=-0.56， 95%CI (-0.96， -0.16)， P=0.006]， decrease BMI [MD=-1.25， 95%CI (-1.51， -0.99)， P<0.001] and body weight [MD= -3.60， 95%CI(-4.24， -2.96)， P<0.001]， increase pulse frequency [MD=2.16， 95%CI (1.51， 2.81)， P<0.001]. The major adverse drug reactions were gastrointestinal reaction； the incidence of gastrointestinal reaction was higher than control group [RD=0.20， 95%CI(0.15，0.26)， P<0.001]， but there was no statistical significance in the incidence of hypoglycemia events between 2 groups [RD=0.00， 95%CI(-0.01，0.02)， P=0.44]. CONCLUSIONS： Semaglutide can significantly decrease HbA1c， FPG， body weight， blood pressure and increase pulse frequency in T2DM patients， and increase the compliance rate of HbA1c. Although the incidence of gastrointestinal reaction is higher than control group， but the risk of hypoglycemia is not higher， indicating Semaglutide is well tolerated and safe., 百拇医药(芦志伟 孙浩 李莹 肖茏珂 董艳 刘爱娜 赵振宇)
关键词 胰高血糖素样肽-1受体激动药；索马鲁肽；2型糖尿病；有效性；安全性；系统评价
Efficacy and Safety of Long-acting GLP-1 Receptor Agonist Semaglutide for Type 2 Diabetes： A Systematic Review
LU Zhiwei1，SUN Hao2，LI Ying1，XIAO Longke1，DONG Yan1，LIU Aina1，ZHAO Zhenyu1(1.Dept. of Pharmacy， Research Institute of Endocrinology， Metabolic Diseases Hospital of Tianjin Medical University/Key Lab of Hormones and Development， Ministry of Public Health， Tianjin 300070， China；2.Dept. of Pharmacy， the Affiliated Hospital of Tianjin Institute for TCM， Tianjin 300020， China)
ABSTRACT OBJECTIVE： To systematically evaluate therapeutic efficacy and safety of long-acting glucagon like peptide-1 (GLP-1) receptor agonist Semaglutide vs. placebo or other glucose-lowering drugs in the treatment of type 2 diabetes mellitus (T2DM)， and to provide evidence-based reference for T2DM in clinic. METHODS： Retrieved from PubMed， Embase， Medline， Cochrane library， randomized controlled trials (RCT) about Semaglutide (trial group) vs. placebo or other glucose-lowering drugs (control group) in the treatment of T2DM were selected during the establishment of database to Sept. 2018. After data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0， Meta-analysis was performed for HbA1c level and compliance rate， fasting plasma glucose (FPG) level， systolic blood pressure (SBP)， diastolic blood pressure (DBP)， body mass index (BMI)， body weight pulse frequency level， the incidence of hypoglycemia and gastrointestinal reaction by using Rev Man 5.3 software. RESULTS： A total of 12 RCTs involving 9 966 patients were included. The results of Meta-analysis showed that compared with control group， trial group could effectively decrease the levels of HbA1c [MD=-1.03， 95%CI(-1.22，-0.85)， P<0.001] and FPG [MD=-1.14， 95%CI(-1.53，-0.76)， P<0.001]， increase compliance rate of HbA1c [RD=0.40， 95%CI(0.31，0.49)， P<0.001]， reduce SBP [MD=-2.61， 95%CI (-3.23， -1.98)， P<0.001] and DBP [MD=-0.56， 95%CI (-0.96， -0.16)， P=0.006]， decrease BMI [MD=-1.25， 95%CI (-1.51， -0.99)， P<0.001] and body weight [MD= -3.60， 95%CI(-4.24， -2.96)， P<0.001]， increase pulse frequency [MD=2.16， 95%CI (1.51， 2.81)， P<0.001]. The major adverse drug reactions were gastrointestinal reaction； the incidence of gastrointestinal reaction was higher than control group [RD=0.20， 95%CI(0.15，0.26)， P<0.001]， but there was no statistical significance in the incidence of hypoglycemia events between 2 groups [RD=0.00， 95%CI(-0.01，0.02)， P=0.44]. CONCLUSIONS： Semaglutide can significantly decrease HbA1c， FPG， body weight， blood pressure and increase pulse frequency in T2DM patients， and increase the compliance rate of HbA1c. Although the incidence of gastrointestinal reaction is higher than control group， but the risk of hypoglycemia is not higher， indicating Semaglutide is well tolerated and safe., 百拇医药(芦志伟 孙浩 李莹 肖茏珂 董艳 刘爱娜 赵振宇)