胰高血糖素样肽1受体激动剂类降糖药致2型糖尿病患者头疼和眩晕的网状Meta分析
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摘要
目的:使用网状Meta分析系统评价胰高血糖素样肽1受体激动剂(GLP-1 RAs)类降糖药对2型糖尿病(T2DM)患者头疼和眩晕的影响。方法:系统检索Medline、Embase、Clinical trials和Cochrane数据库中(截止2017年6月23日)比较GLP-1 RAs与传统降糖药或安慰剂对头疼和眩晕发生风险影响的随机对照试验(RCT),采用贝叶斯网状Meta分析对纳入的研究进行分析。结果:共纳入100项RCTs,包括15种干预措施:8种GLP-1 RAs类降糖药(艾塞那肽、艾塞那肽缓释剂、利拉鲁肽、利西拉来、他司鲁肽、阿必鲁肽、杜拉鲁肽、索玛鲁肽)、安慰剂、2种二肽基肽酶-4(DPP-4)抑制剂(西格列汀和维格列汀)和4种传统降糖药(胰岛素、二甲双胍、磺脲类、噻唑烷二酮类)。网状Meta分析结果显示:与胰岛素相比,艾塞那肽(OR=1.35,95%CI:1.13~1.60)、利拉鲁肽(OR=1.35,95%CI:1.12~1.62)、利西拉来(OR=1.59,95%CI:1.22~2.06)和他司鲁肽(OR=1.78,95%CI:1.33~2.37)致T2DM患者发生头疼的风险增加;与安慰剂、胰岛素及噻唑烷二酮相比,艾塞那肽和利拉鲁肽显著增加了眩晕发生的风险(OR的取值范围为1.56~2.56)。此外,后验概率显示,致T2DM患者发生头疼风险最高的前三位为艾塞那肽缓释剂、二甲双胍、他司鲁肽;致T2DM患者发生眩晕风险最高的前三位为利拉鲁肽、利西拉来和艾塞那肽。结论:艾塞那肽缓释剂和他司鲁肽显著增加了头疼的发生风险,利拉鲁肽显著增加了眩晕的发生风险,但仍建议开展相应的大型前瞻性研究加以验证。
Objective: To systematically review the effects of Glucagon-like peptide-1 receptor agonists( GLP-1 RAs) on headache and dizziness among type 2 diabetes( T2DM) patients. Methods: Medline,Embase,Clinical trials and Cochrane library were searched from inception through June 23,2017 to identify randomized clinical trials( RCTs) assessing safety of GLP-1 RAs versus placebo or other anti-diabetic drugs in T2DM. Network Meta-analysis within a Bayesian framework was performed to calculate odds ratios for the incidence of headache and dizziness. Results: In the study,100 RCTs were included,including 15 treatments: 8 GLP-1 RAs( exenatide,exenatide-long-release-agent,liraglutide,lixisenatide,taspoglutide,albiglutide,dulaglutide and semaglutide),placebo,2 dipeptidyl peptidase-4 inhibitors( sitagliptin and vildagliptin) and 4 traditional anti-diabetic drugs( insulin,metformin,sulfonylureas and thiazolidinediones ketones( TZD)). Compared with insulin,exenatide,liraglutide,lixisenatide and taspoglutide significantly increased the incidence of headache,with OR of 1. 35( 95% CI: 1. 13-1. 60),1. 35( 95% CI: 1. 12-1. 62),1. 59( 95% CI: 1. 22-2. 06) and 1. 78( 95% CI: 1. 33-2. 37),respectively. Significant lowering effects on dizziness were found when liraglutide and exenatide versus placebo,insulin,TZD( range of ORs: 1. 56-2. 56). The result from the network Meta-analysis based on Bayesian theory could be used to rank all the treatments included,which showed that taspoglutide ranked third with maximum risk on headache,liraglutide ranked first with maximum risk on dizziness. Conclusion: Exenatide-long-release-agent and taspoglutide were associated with significantly increasing effect on headache,liraglutide was associated with significantly increasing effect on dizziness.
Objective: To systematically review the effects of Glucagon-like peptide-1 receptor agonists( GLP-1 RAs) on headache and dizziness among type 2 diabetes( T2DM) patients. Methods: Medline,Embase,Clinical trials and Cochrane library were searched from inception through June 23,2017 to identify randomized clinical trials( RCTs) assessing safety of GLP-1 RAs versus placebo or other anti-diabetic drugs in T2DM. Network Meta-analysis within a Bayesian framework was performed to calculate odds ratios for the incidence of headache and dizziness. Results: In the study,100 RCTs were included,including 15 treatments: 8 GLP-1 RAs( exenatide,exenatide-long-release-agent,liraglutide,lixisenatide,taspoglutide,albiglutide,dulaglutide and semaglutide),placebo,2 dipeptidyl peptidase-4 inhibitors( sitagliptin and vildagliptin) and 4 traditional anti-diabetic drugs( insulin,metformin,sulfonylureas and thiazolidinediones ketones( TZD)). Compared with insulin,exenatide,liraglutide,lixisenatide and taspoglutide significantly increased the incidence of headache,with OR of 1. 35( 95% CI: 1. 13-1. 60),1. 35( 95% CI: 1. 12-1. 62),1. 59( 95% CI: 1. 22-2. 06) and 1. 78( 95% CI: 1. 33-2. 37),respectively. Significant lowering effects on dizziness were found when liraglutide and exenatide versus placebo,insulin,TZD( range of ORs: 1. 56-2. 56). The result from the network Meta-analysis based on Bayesian theory could be used to rank all the treatments included,which showed that taspoglutide ranked third with maximum risk on headache,liraglutide ranked first with maximum risk on dizziness. Conclusion: Exenatide-long-release-agent and taspoglutide were associated with significantly increasing effect on headache,liraglutide was associated with significantly increasing effect on dizziness.
引文
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2 汪会琴,胡如英,武海滨,等.2型糖尿病报告发病率研究进展[J].浙江预防医学,2016,28(1):37-39
3 林旋,王俊玲,李泰明,等.长效胰高血糖素样肽-1受体激动剂的研究进展[J].中国新药杂志,2015,24(15):1735-1741
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5 Nauck M.Incretin therapies:highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors[J].Diabetes Obes Metab,2016,18(3):203-216
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7 张婉珠,梁斌鑫,王维.降糖药的研究现状及新进展[J].医药导报,2013,32(11):1455-1458
8 Karagiannis T,Liakos A,Bekiari E,et al.Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes:a systematic review and meta-analysis of randomized controlled trials[J].Diabetes Obes Metab,2015,17(11):1065-1074
9 Pinelli NR,Hurren KM.Efficacy and safety of long-acting glucagon-like peptide-1 receptor agonists compared with exenatide twice daily and sitagliptin in type 2 diabetes mellitus:a systematic review and meta-analysis[J].Ann Pharmacother,2011,45(7-8):850-860
10 Filippatos TD,Panagiotopoulou TV,Elisaf MS.Adverse Effects of GLP-1 Receptor Agonists[J].Rev Diabet Stud,2014,11(3-4):202-230
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13 Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[EB/OL].(2011-03)[2017-10]http:∥www.cochrane-handbook.org
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15 Seshasai SR,Bennett RL,Petrie JR,et al.Cardiovascular safety of the glucagon-like peptide-1 receptor agonist taspoglutide in people with type 2 diabetes:an individual participant data meta-analysis of randomized controlled trials[J].Diabetes Obes Metab,2015,17(5):505-510
16 Su B,Sheng H,Zhang M,et al.Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists'treatment:a meta-analysis of randomized controlled trials[J].Endocrine,2015,48(1):107-115
17 Li ZX,Wu SS,Yang ZR,et al.[Impact of glucagon-like peptide-1 receptor agonists on nasopharyngitis and upper respiratory tract infection among patients with type 2 diabetes:a network meta-analysis][J].Beijing Da Xue Xue Bao,2016,48(3):454-459
18 Raz I,Fonseca V,Kipnes M,et al.Efficacy and safety of taspoglutide monotherapy in drug-naive type 2 diabetic patients after 24 weeks of treatment:results of a randomized,double-blind,placebo-controlled phase 3 study(T-emerge1)[J].Diabetes Care,2012,35(3):485-487
19 Rosenstock J,Balas B,Charbonnel B,et al.The fate of taspoglutide,a weekly GLP-1 receptor agonist,versus twicedaily exenatide for type 2 diabetes:the T-emerge 2 trial[J].Diabetes Care,2013,36(3):498-504
20 Henry RR,Mudaliar S,Kanitra L,et al.Efficacy and safety of taspoglutide in patients with type 2 diabetes inadequately controlled with metformin plus pioglitazone over 24 weeks:T-Emerge 3 trial[J].J Clin Endocrinol Metab,2012,97(7):2370-2379
21 Bergenstal RM,Forti A,Chiasson JL,et al.Efficacy and safety of taspoglutide versus sitagliptin for type 2 diabetes mellitus(T-emerge 4 trial)[J].Diabetes Ther,2012,3(1):13
22 Nauck M,Horton E,Andjelkovic M,et al.Taspoglutide,a once-weekly glucagon-like peptide 1 analogue,vs.insulin glargine titrated to target in patients with type 2 diabetes:an open-label randomized trial[J].Diabet Med,2013,30(1):109-113
23 Pratley RE,Urosevic D,Boldrin M,et al.Efficacy and tolerability of taspoglutide versus pioglitazone in subjects with type 2 diabetes uncontrolled with sulphonylurea or sulphonylurea-metformin therapy:a randomized,double-blind study(T-emerge 6)[J].Diabetes Obes Metab,2013,15(3):234-240
24 Hollander P,Lasko B,Barnett AH,et al.Effects of taspoglutide on glycemic control and body weight in obese patients with type 2 diabetes(T-emerge 7 study)[J].Obesity(Silver Spring),2013,21(2):238-247
25 胡丽华,陈文广,吴雪莲.老年糖尿病与脑动脉硬化的关系[J].心血管康复医学杂志.2003,12(3):219-221
26 Gerrity RG,Natarajan R,Nadler JL,et al.Diabetes-induced accelerated atherosclerosis in swine[J].Diabetes,2001,50(7):1654-1665
27 Renard CB,Kramer F,Johansson F,et al.Diabetes and diabetes-associated lipid abnormalities have distinct effects on initiation and progression of atherosclerotic lesions[J].J Clin Invest,2004,114(5):659-668
28 刘荣祯,张天燕,李欣,等.高压氧对脑动脉硬化性眩晕的临床疗效[J].中国康复理论与实践,2013,19(7):674-675
29 Umpierrez GE,Kitabchi AE.Diabetic ketoacidosis:risk factors and management strategies[J].Treat Endocrinol,2003,2(2):95-108
30 尹延伟,胡爱民,刘宏利,等.糖尿病酮症酸中毒相关危险因素分析[J].临床急诊杂志,2012,13(2):94-96
31 Gutzwiller JP,Tschopp S,Bock A,et al.Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men[J].J Clin Endocrinol Metab,2004,89(6):3055-3061
32 Vilsboll T.Liraglutide:a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus[J].Expert Opin Investig Drugs,2007,16(2):231-237
2 汪会琴,胡如英,武海滨,等.2型糖尿病报告发病率研究进展[J].浙江预防医学,2016,28(1):37-39
3 林旋,王俊玲,李泰明,等.长效胰高血糖素样肽-1受体激动剂的研究进展[J].中国新药杂志,2015,24(15):1735-1741
4 White WB,Baker WL.Cardiovascular effects of incretinbased therapies[J].Annu Rev Med,2016,67:245-260
5 Nauck M.Incretin therapies:highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors[J].Diabetes Obes Metab,2016,18(3):203-216
6 Drucker DJ,Nauck MA.The incretin system:glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes[J].Lancet,2006,368(9548):1696-1705
7 张婉珠,梁斌鑫,王维.降糖药的研究现状及新进展[J].医药导报,2013,32(11):1455-1458
8 Karagiannis T,Liakos A,Bekiari E,et al.Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes:a systematic review and meta-analysis of randomized controlled trials[J].Diabetes Obes Metab,2015,17(11):1065-1074
9 Pinelli NR,Hurren KM.Efficacy and safety of long-acting glucagon-like peptide-1 receptor agonists compared with exenatide twice daily and sitagliptin in type 2 diabetes mellitus:a systematic review and meta-analysis[J].Ann Pharmacother,2011,45(7-8):850-860
10 Filippatos TD,Panagiotopoulou TV,Elisaf MS.Adverse Effects of GLP-1 Receptor Agonists[J].Rev Diabet Stud,2014,11(3-4):202-230
11 Ades AE,Sculpher M,Sutton A,et al.Bayesian methods for evidence synthesis in cost-effectiveness analysis[J].Pharmacoeconomics,2006,24(1):1-19
12 Lu G,Ades AE.Combination of direct and indirect evidence in mixed treatment comparisons[J].Stat Med,2004,23(20):3105-3124
13 Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[EB/OL].(2011-03)[2017-10]http:∥www.cochrane-handbook.org
14 Prasad-Reddy L,Isaacs D.A clinical review of GLP-1 receptor agonists:efficacy and safety in diabetes and beyond[J].Drugs Context,2015,4:212283
15 Seshasai SR,Bennett RL,Petrie JR,et al.Cardiovascular safety of the glucagon-like peptide-1 receptor agonist taspoglutide in people with type 2 diabetes:an individual participant data meta-analysis of randomized controlled trials[J].Diabetes Obes Metab,2015,17(5):505-510
16 Su B,Sheng H,Zhang M,et al.Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists'treatment:a meta-analysis of randomized controlled trials[J].Endocrine,2015,48(1):107-115
17 Li ZX,Wu SS,Yang ZR,et al.[Impact of glucagon-like peptide-1 receptor agonists on nasopharyngitis and upper respiratory tract infection among patients with type 2 diabetes:a network meta-analysis][J].Beijing Da Xue Xue Bao,2016,48(3):454-459
18 Raz I,Fonseca V,Kipnes M,et al.Efficacy and safety of taspoglutide monotherapy in drug-naive type 2 diabetic patients after 24 weeks of treatment:results of a randomized,double-blind,placebo-controlled phase 3 study(T-emerge1)[J].Diabetes Care,2012,35(3):485-487
19 Rosenstock J,Balas B,Charbonnel B,et al.The fate of taspoglutide,a weekly GLP-1 receptor agonist,versus twicedaily exenatide for type 2 diabetes:the T-emerge 2 trial[J].Diabetes Care,2013,36(3):498-504
20 Henry RR,Mudaliar S,Kanitra L,et al.Efficacy and safety of taspoglutide in patients with type 2 diabetes inadequately controlled with metformin plus pioglitazone over 24 weeks:T-Emerge 3 trial[J].J Clin Endocrinol Metab,2012,97(7):2370-2379
21 Bergenstal RM,Forti A,Chiasson JL,et al.Efficacy and safety of taspoglutide versus sitagliptin for type 2 diabetes mellitus(T-emerge 4 trial)[J].Diabetes Ther,2012,3(1):13
22 Nauck M,Horton E,Andjelkovic M,et al.Taspoglutide,a once-weekly glucagon-like peptide 1 analogue,vs.insulin glargine titrated to target in patients with type 2 diabetes:an open-label randomized trial[J].Diabet Med,2013,30(1):109-113
23 Pratley RE,Urosevic D,Boldrin M,et al.Efficacy and tolerability of taspoglutide versus pioglitazone in subjects with type 2 diabetes uncontrolled with sulphonylurea or sulphonylurea-metformin therapy:a randomized,double-blind study(T-emerge 6)[J].Diabetes Obes Metab,2013,15(3):234-240
24 Hollander P,Lasko B,Barnett AH,et al.Effects of taspoglutide on glycemic control and body weight in obese patients with type 2 diabetes(T-emerge 7 study)[J].Obesity(Silver Spring),2013,21(2):238-247
25 胡丽华,陈文广,吴雪莲.老年糖尿病与脑动脉硬化的关系[J].心血管康复医学杂志.2003,12(3):219-221
26 Gerrity RG,Natarajan R,Nadler JL,et al.Diabetes-induced accelerated atherosclerosis in swine[J].Diabetes,2001,50(7):1654-1665
27 Renard CB,Kramer F,Johansson F,et al.Diabetes and diabetes-associated lipid abnormalities have distinct effects on initiation and progression of atherosclerotic lesions[J].J Clin Invest,2004,114(5):659-668
28 刘荣祯,张天燕,李欣,等.高压氧对脑动脉硬化性眩晕的临床疗效[J].中国康复理论与实践,2013,19(7):674-675
29 Umpierrez GE,Kitabchi AE.Diabetic ketoacidosis:risk factors and management strategies[J].Treat Endocrinol,2003,2(2):95-108
30 尹延伟,胡爱民,刘宏利,等.糖尿病酮症酸中毒相关危险因素分析[J].临床急诊杂志,2012,13(2):94-96
31 Gutzwiller JP,Tschopp S,Bock A,et al.Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men[J].J Clin Endocrinol Metab,2004,89(6):3055-3061
32 Vilsboll T.Liraglutide:a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus[J].Expert Opin Investig Drugs,2007,16(2):231-237