塞马鲁肽治疗2型糖尿病疗效与安全性的Meta分析
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摘要
目的评价塞马鲁肽治疗2型糖尿病的疗效与安全性。方法检索PubMed、 Embase、 Cochrane图书馆、中国知网、万方和维普数据库,检索时限从建库至2018年7月,纳入塞马鲁肽0.5、 1 mg对比安慰剂或阳性药(对照组)治疗2型糖尿病的随机对照试验(RCT)。采用RevMan 5.3软件对疗效和安全性指标进行Meta分析,按Cochrane系统评价手册进行质量评估,漏斗图检测发表偏倚。结果纳入8篇RCT,包括6 006例患者。与对照组比较,塞马鲁肽0.5 mg和1 mg组糖化血红蛋白(HbA1c)均显著降低(MD=-0.93%, 95%CI:-1.24%～-0.61%, P <0.01; MD=-1.12%, 95%CI:-1.42%～-0.81%, P <0.01),同时空腹血糖(FPG)、体重和收缩压(SBP)显著降低(P <0.01), HbA1c<7%达标例数增加(P <0.01);组间比较,塞马鲁肽1 mg组FPG、体重和SBP显著低于塞马鲁肽0.5 mg组(P <0.01)。安全性方面,与对照组比较,塞马鲁肽0.5 mg和1 mg组因不良事件退出例数、胃肠道不良事件发生率显著增加(P <0.01),但严重不良事件发生率无显著差异(P> 0.05);塞马鲁肽1 mg组因不良事件退出例数和呕吐发生率显著高于0.5 mg组(P <0.05),其他胃肠道不良事件发生率均无显著差异(P> 0.05)。结论塞马鲁肽治疗2型糖尿病有较好的疗效,且1 mg疗效优于0.5 mg,严重不良事件少,但应注意胃肠道不良事件。
AIM To evaluate the efficacy and safety of semaglutide in treatment of type 2 diabetes( T2DM). METHODS The randomized controlled trials( RCTs) of semaglutide 0.5, 1 mg compared with placebo or positive agents( control group) in the treatment of T2DM were selected in PubMed, Embase,Cochrane Library, CNKI, Wanfang and VIP databases from inception to July, 2018. Meta-analysis of efficacy and safety was performed by RevMan 5.3. Quality assessment was evaluated by the Cochrane handbook.Publication bias was detected using a funnel plot. RESULTS Eight RCTs including 6 006 patients were included.Compared with the control group, the glycosylated hemoglobin( HbA1c) were significantly decreased in the semaglutide 0.5 mg and 1 mg groups(MD =-0.93%, 95%CI:-1.24%--0.61%, P < 0.01; MD =-1.12%,95%CI:-1.42%--0.81%, P < 0.01). While fasting blood glucose( FPG), body weight and systolic blood pressure(SBP) were significantly lower(P < 0.01), and the number of patients achieving HbA1 c< 7% were increased significantly(P < 0.01). FPG, body weight and SBP in the semaglutide 1 mg group were significantly lower than those in the semaglutide 0.5 mg group( P < 0.01). In terms of safety, compared with the control group, the number of patients withdrawal because of adverse events and the incidence of gastrointestinal disorders were significantly increased in the semaglutide 0.5 mg and 1 mg groups(P < 0.01), but the incidence of serious adverse events was no significantly different(P > 0.05). The number of patients withdrawal because of adverse events and incidence of vomiting in the semaglutide 1 mg group were higher than those in the 0.5 mg group(P < 0.05). There was no significant difference in the incidence of other gastrointestinal disorders(P >0.05). CONCLUSION Semaglutide has good efficacy of T2DM, and 1 mg is superior to 0.5 mg. There are fewer serious adverse events, but the gastrointestinal disorders are increased.
AIM To evaluate the efficacy and safety of semaglutide in treatment of type 2 diabetes( T2DM). METHODS The randomized controlled trials( RCTs) of semaglutide 0.5, 1 mg compared with placebo or positive agents( control group) in the treatment of T2DM were selected in PubMed, Embase,Cochrane Library, CNKI, Wanfang and VIP databases from inception to July, 2018. Meta-analysis of efficacy and safety was performed by RevMan 5.3. Quality assessment was evaluated by the Cochrane handbook.Publication bias was detected using a funnel plot. RESULTS Eight RCTs including 6 006 patients were included.Compared with the control group, the glycosylated hemoglobin( HbA1c) were significantly decreased in the semaglutide 0.5 mg and 1 mg groups(MD =-0.93%, 95%CI:-1.24%--0.61%, P < 0.01; MD =-1.12%,95%CI:-1.42%--0.81%, P < 0.01). While fasting blood glucose( FPG), body weight and systolic blood pressure(SBP) were significantly lower(P < 0.01), and the number of patients achieving HbA1 c< 7% were increased significantly(P < 0.01). FPG, body weight and SBP in the semaglutide 1 mg group were significantly lower than those in the semaglutide 0.5 mg group( P < 0.01). In terms of safety, compared with the control group, the number of patients withdrawal because of adverse events and the incidence of gastrointestinal disorders were significantly increased in the semaglutide 0.5 mg and 1 mg groups(P < 0.01), but the incidence of serious adverse events was no significantly different(P > 0.05). The number of patients withdrawal because of adverse events and incidence of vomiting in the semaglutide 1 mg group were higher than those in the 0.5 mg group(P < 0.05). There was no significant difference in the incidence of other gastrointestinal disorders(P >0.05). CONCLUSION Semaglutide has good efficacy of T2DM, and 1 mg is superior to 0.5 mg. There are fewer serious adverse events, but the gastrointestinal disorders are increased.
引文
[1]INZUCCHI SE,BERGENSTAL RM,BUSE JB,et al.Management of hyperglycemia in type 2 diabetes,2015:a patient-centered approach:update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes[J].Diabetes Care,2015,38(1):140-149.
[2]段小云,冯碧敏,张成斌,等.阿格列汀与其他口服降糖药比较治疗2型糖尿病的系统评价[J].中国新药与临床杂志,2017,36(4):226-233.
[3]INZUCCHI SE,BERGENSTAL RM,BUSE JB,et al.Management of hyperglycemia in type 2 diabetes:a patientcentered approach:position statement of the American Diabetes Association(ADA)and the European Association for the Study of Diabetes(EASD)[J].Diabetes Care,2012,35(6):1364-1379.
[4]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2017年版)[J].中华糖尿病杂志,2018,10(1):4-67.
[5]朱依谆,殷明.药理学[M].北京:人民卫生出版社,2011:390-391.
[6]The Cochrane Collaboration.Cochrane handbook for systematic reviews of interventions[EB/OL].(2011-03)[2016-08].http://handbook.cochrane.org/.
[7]AHREN B,MASMIQUEL L,KUMAR H,et al.Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin,thiazolidinediones,or both,in patients with type 2 diabetes(SUSTAIN 2):a 56-week,doubleblind,phase 3a,randomised trial[J].Lancet Diabetes Endocrinol,2017,5(5):341-354.
[8]SORLI C,HARASHIMA SI,TSOUKAS GM,et al.Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes(SUSTAIN 1):a double-blind,randomised,placebo-controlled,parallel-group,multinational,multicentre phase 3a trial[J].Lancet Diabetes Endocrinol,2017,5(4):251-260.
[9]RODBARD HW,LINGVAY I,REED J,et al.Semaglutide added to basal insulin in type 2 diabetes(SUSTAIN 5):a randomized,controlled trial[J].J Clin Endocrinol Metab,2018,103(6):2291-2301.
[10]AHMANN AJ,CAPEHORN M,CHARPENTIER G,et al.Efficacy and safety of once-weekly semaglutide versus exenatide er in subjects with type 2 diabetes(SUSTAIN 3):a 56-week,open-label,randomized clinical trial[J].Diabetes Care,2018,41(2):258-266.
[11]ARODA VR,BAIN SC,CARIOU B,et al.Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin(with or without sulfonylureas)in insulinnaive patients with type 2 diabetes(SUSTAIN 4):a randomised,open-label,parallel-group,multicentre,multinational,phase3a trial[J].Lancet Diabetes Endocrinol,2017,5(5):355-366.
[12]KAKU K,YAMADA Y,WATADA H,et al.Safety and efficacy of once-weekly semaglutide vs additional oral antidiabetic drugs in Japanese people with inadequately controlled type 2 diabetes:a randomized trial[J].Diabetes Obes Metab,2018,20(5):1202-1212.
[13]SEINO Y,TERAUCHI Y,OSONOI T,et al.Safety and efficacy of semaglutide once weekly vs sitagliptin once daily,both as monotherapy in Japanese people with type 2 diabetes[J].Diabetes Obes Metab,2018,20(2):378-388.
[14]PRATLEY RE,ARODA VR,LINGVAY I,et al.Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes(SUSTAIN 7):a randomised,open-label,phase 3b trial[J].Lancet Diabetes Endocrinol,2018,6(4):275-286.
[15]LAU J,BLOCH P,SCHAFFER L,et al.Discovery of the onceweekly glucagon-like peptide-1(GLP-1)analogue semaglutide[J].J Med Chem,2015,58(18):7370-7380.
[16]朱翊,封宇飞.GLP-1受体激动剂索马鲁肽的药理与临床评价[J].临床药物治疗杂志,2018,16(3):17-27.
[17]DHILLON S.Semaglutide:first global approval[J].Drugs,2018,78(2):275-284.
[2]段小云,冯碧敏,张成斌,等.阿格列汀与其他口服降糖药比较治疗2型糖尿病的系统评价[J].中国新药与临床杂志,2017,36(4):226-233.
[3]INZUCCHI SE,BERGENSTAL RM,BUSE JB,et al.Management of hyperglycemia in type 2 diabetes:a patientcentered approach:position statement of the American Diabetes Association(ADA)and the European Association for the Study of Diabetes(EASD)[J].Diabetes Care,2012,35(6):1364-1379.
[4]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2017年版)[J].中华糖尿病杂志,2018,10(1):4-67.
[5]朱依谆,殷明.药理学[M].北京:人民卫生出版社,2011:390-391.
[6]The Cochrane Collaboration.Cochrane handbook for systematic reviews of interventions[EB/OL].(2011-03)[2016-08].http://handbook.cochrane.org/.
[7]AHREN B,MASMIQUEL L,KUMAR H,et al.Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin,thiazolidinediones,or both,in patients with type 2 diabetes(SUSTAIN 2):a 56-week,doubleblind,phase 3a,randomised trial[J].Lancet Diabetes Endocrinol,2017,5(5):341-354.
[8]SORLI C,HARASHIMA SI,TSOUKAS GM,et al.Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes(SUSTAIN 1):a double-blind,randomised,placebo-controlled,parallel-group,multinational,multicentre phase 3a trial[J].Lancet Diabetes Endocrinol,2017,5(4):251-260.
[9]RODBARD HW,LINGVAY I,REED J,et al.Semaglutide added to basal insulin in type 2 diabetes(SUSTAIN 5):a randomized,controlled trial[J].J Clin Endocrinol Metab,2018,103(6):2291-2301.
[10]AHMANN AJ,CAPEHORN M,CHARPENTIER G,et al.Efficacy and safety of once-weekly semaglutide versus exenatide er in subjects with type 2 diabetes(SUSTAIN 3):a 56-week,open-label,randomized clinical trial[J].Diabetes Care,2018,41(2):258-266.
[11]ARODA VR,BAIN SC,CARIOU B,et al.Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin(with or without sulfonylureas)in insulinnaive patients with type 2 diabetes(SUSTAIN 4):a randomised,open-label,parallel-group,multicentre,multinational,phase3a trial[J].Lancet Diabetes Endocrinol,2017,5(5):355-366.
[12]KAKU K,YAMADA Y,WATADA H,et al.Safety and efficacy of once-weekly semaglutide vs additional oral antidiabetic drugs in Japanese people with inadequately controlled type 2 diabetes:a randomized trial[J].Diabetes Obes Metab,2018,20(5):1202-1212.
[13]SEINO Y,TERAUCHI Y,OSONOI T,et al.Safety and efficacy of semaglutide once weekly vs sitagliptin once daily,both as monotherapy in Japanese people with type 2 diabetes[J].Diabetes Obes Metab,2018,20(2):378-388.
[14]PRATLEY RE,ARODA VR,LINGVAY I,et al.Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes(SUSTAIN 7):a randomised,open-label,phase 3b trial[J].Lancet Diabetes Endocrinol,2018,6(4):275-286.
[15]LAU J,BLOCH P,SCHAFFER L,et al.Discovery of the onceweekly glucagon-like peptide-1(GLP-1)analogue semaglutide[J].J Med Chem,2015,58(18):7370-7380.
[16]朱翊,封宇飞.GLP-1受体激动剂索马鲁肽的药理与临床评价[J].临床药物治疗杂志,2018,16(3):17-27.
[17]DHILLON S.Semaglutide:first global approval[J].Drugs,2018,78(2):275-284.