噻唑烷二酮类药物治疗代谢综合征的系统评价_《中国循证医学杂志》

作者：

1. 四川大学华西医院GCP中心（成都 610041）2. 四川大学华西医院内分泌科（成都 610041）3. 四川大学华西医院中国循证医学中心（成都 610041）;

关键词：

代谢综合征噻唑烷二酮类罗格列酮吡格列酮系统评价随机对照试验

DOI：

10.7507/1672-2531.20090105

视频：

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摘要 全文 图表 视频 参考文献 施引文献 补充材料

目的　系统评价噻唑烷二酮类药物治疗代谢综合征的有效性和安全性。
方法　运用系统评价的方法，计算机检索Cochrane 图书馆（2007 年，第4 期）、MEDLINE（1966 ～ 2007）、EMbase（1984 ～ 2007）、中国生物医学文献数据库（1978 ～ 2007）、中国学术期刊全文数据库（1979 ～ 2007）和中文科技期刊全文数据库（1989 ～ 2007），并手工检索《中华内分泌代谢杂志》等相关杂志，收集噻唑烷二酮类（TZDs）药物治疗代谢综合征的随机或半随机对照试验（RCT）。按Cochrane 系统评价标准评价纳入研究质量，对同质研究采用RevMan 软件进行Meta 分析，对不能进行Meta 分析的数据，则只进行描述性的定性分析。
结果　共纳入10 个RCT，包括1 183 例MS 患者。由于大多数研究间存在临床异质性，故仅对个别研究进行了Meta 分析。5 个研究进行了罗格列酮与安慰剂比较，但仅1 个研究报告了心血管事件（心肌梗死、冠状动脉血管重建术）发生率，结果显示两组差异无统计学意义［RR= 0.50，95%CI（0.25，1.00）］；罗格列酮减少代谢综合征患者例数及对稳态模型胰岛素抵抗指数（HOMA-index）的改善优于安慰剂，而二者对TG、HDL-c 的影响差异则无统计学意义。与安慰剂比较，吡格列酮对HOMA-index、QUICKI、SBP、HDL-c 的改善优于安慰剂；二者对TG 的影响差异无统计学意义。吡格列酮+ 格列美脲与罗格列酮+ 格列美脲比较，两者对HOMA-index、SBP/DBP、FPG、PPG 和HbA1c 的影响，其差异无统计学意义；罗格列酮+ 格列美脲对HDL-c 无影响，而对TG、HDL-c 的改善吡格列酮+ 格列美脲优于罗格列酮+ 格列美脲。与格列美脲+ 二甲双胍比较，罗格列酮+ 二甲双胍对HOMA-index、SBP/DBP、HDL-c、TG 的改善优于格列美脲+ 二甲双胍，但二者对FPG、PPG、HbA1c 的影响差异无统计学意义。罗格列酮+ 二甲双胍与吡格列酮+ 二甲双胍比较，两者对HOMAindex、FPG、PPG、HbA1c 的影响差异无统计学意义；罗格列酮+ 二甲双胍对TG、HDL-c 无影响，吡格列酮+ 二甲双胍对TG、HDL-c 的改善优于罗格列酮+ 二甲双胍。常规治疗加用罗格列酮与不加用罗格列酮比较，常规治疗加用罗格列酮对HOMA-index、SBP/DBP 的改善优于常规治疗。罗格列酮、吡格列酮对体重指数和腰围无改善或使二者增高。有9 个研究报道了不良反应，结果显示TZDs 耐受性良好，不良反应为轻至中度，无严重不良反应。
结论　TZDs 与安慰剂比较能提高MS 患者胰岛素的敏感性；吡格列酮对HDL-c 的改善优于罗格列酮；TZDs 对血压的疗效不确定；目前尚未发现罗格列酮对TG、HDL-c 有影响；TZDs 对肥胖指标无改善，或有负性影响。由于上述结论基本来自单个研究，研究质量参差不齐，大多数研究样本量小，因此使用结论时必须谨慎。由于对心血管事件、MS 患者比率影响的研究少、质量不高，目前TZDs 对心血管事件、MS 患者比率的疗效还难以得出结论。目前尚无足够的证据证明哪种药物更有效，期待开展更多高质量、大样本、长期随访的RCT，以提供更可靠的证据。

引用本文： 勾忠平,李秀钧,吴泰相. 噻唑烷二酮类药物治疗代谢综合征的系统评价. 中国循证医学杂志, 2009, 09(5): 574-583. doi: 10.7507/1672-2531.20090105 复制

1.	responsiveness to its antidiabetic effect. Diabets Care, 2003, 26(9): 2493-2499.
2.	Metabolic Syndrome Treated with Glimepiride: A Twelve-Month, Multicenter, Double-Blind, Randomized, Controlled, Parallel-Group Trial. Clinical Therapeutics, 2004, 26(5): 746-754.
3.	Douglas JA, Erdos MR, Watanabe RM, et al. The Peroxisome Proliferator–Activated Receptor- 2 Pro12Ala Variant: Association With Type 2 Diabetes and Trait Differences. Diabetes, 2001, 50(4): 886- 890.
4.	Viberti G, Kahn SE, Greene DA, et al. A Diabetes Outcome Progression Trial (ADOPT): An international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. Diabetes Care, 2002, 25(10): l737- l743.
5.	MartensF M, VisserenF L, LemayJ, et al. Metabolic and additional vascular effects of thiazolidinediones. Drug, 2002, 62(10): 1463-1480.
6.	徐成斌. 代谢综合征. 国外医学内分泌学分册. 2005, 25(1): 3-6.
7.	Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trail. Lancet, 2005, 366(9493): 1279-1289.
8.	Marx N & Hombach V. Peroxisome proliferator-activated receptors (PPARs) in the vessel wall: new regulators of gene expression in vascular cells (in German). Zeitschrift für Kardiologie, 2001, 90(7): 470-477.
9.	Goetze S, XI XP, Kawano H, et al. PPAR gamma-ligands inhibit migration mediated by multiple chemoattractants in vascular smooth muscle cells. Journal of Cardiovascular Pharmacology, 1999, 33(5): 798-806.
10.	Jiang C, Ting AT, Seed B. PPAR-agonists inhibit production of monocyte inflammatory cytokines. Nature, 1998, 391(6662): 82-86.
11.	Chinetti G, Griglio S, Antonucci M, et al. Activation of proliferatoractivated receptors and induces apoptosis of human monocytederived macrophages. J Biol Chem, 1998, 273(40): 25573-25580.
12.	Koshi y ama H, Shimono D, Kuwamur a N, et al . Rapid communication: inhibitory effect of pioglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab, 2001, 86(7): 3452-3456.
13.	Satoh N, Ogawa Y, Usul T, et al. Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the.
14.	Haffner SM, Greenberg AS, Weston WM, et al. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation, 2002, 106(6): 679-684.
15.	Pfutzner A, Marx N, Lubben G, et al. Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the pioneer study. J Am Coll Cardiol, 2005, 45(12): 1925-1931.
16.	Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care, 2005, 28(7): 1547-1554.
17.	Fullert S, Schneider F, Haak E, et al. Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind, placebocontrolled study. J Clin Endocrinol Metab, 2002, 87(12): 5503-5506.
18.	Raji A, Williams GH, Seely EW, et al. Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients. Diabetes Care, 2003, 26(1): 172-178.
19.	Alberti KGMM, Zimmet PZ, WHO Consultation. Definition,diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med, 1998, 15(7): 539-553.
20.	Expert Panel on Detection, Evaluation, and Treatment of High Blood cholesterol in Adults (Adult treatment Panel Ⅲ). Executive summary of the third report of the National Cholesteral Eduation Program (NECP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. J Am Med Assoc, 2001, 285(19): 2486-2497.
21.	Barclay L. Medscape Medical News. New definition of the metabolic syndrome: a newsmaker interview with Sir George Alberti, MA, DPhil, BMBCh. Available at: http: //www. medscape. com/viewarticle/504382 Accessed July 8, 2005.
22.	吴泰相, 刘关键. 隐蔽分组（分配隐藏）和盲法的概念、实施与报告. 中国循证医学杂志, 2007, 7(3): 222-225.
23.	Cao Z, Zhou YJ, Zhao YX, et al. Rosiglitazone could improve clinical outcome after coronary stent implantation in nondiabetes patients with metabolic syndrome. Chinese Medical Journal, 2006, 119(14): 1171-1175.
24.	Samaha FF, Szapary PO, Iqbal N, et al. Effects of Rosiglitazone on Lipids, Adipokines, and Inflammatory Markers in Nondiabetic Patients With Low High-Density Lipoprotein Cholesterol and Metabolic Syndrome. Arterioscler Thromb Vasc Biol, 2006, 26(3): 624-630.
25.	Derosa G, Cicero AFG, Gaddi A, et al. Metabolic Effects of Pioglitazone and Rosiglitazone in Patients with Diabetes and.
26.	Derosa G, Gaddi AV, Ciccarelli L, et al. Long-term effect of glimepiride and rosiglitazone on non-conventional cardiovascular risk factors in metformin-treated patients affected by metabolic syndrome: a randomized, double-blind clinical trial. The journal of international medical resesarch, 2005, 33(3): 284-294.
27.	Derosa G, D’Angelo A, Ragonesi PD, et al. Metformin–pioglitazone and metformin- rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndrome. Journal of Clinical Pharmacy and Therapeutics, 2006, 31(4): 375-383.
28.	Esposito K, Ciotola M, Carleo D, et al. Effect of Rosiglitazone on Endothelial Function and Inflammatory Markers in Patients With the Metabolic Syndrome. Diabetes Care, 2006, 29(5): 1071-1076.
29.	Szapary PO, Bloedon LT, Samaha FF, et al. Effects of Pioglitazone on Lipoproteins, Inflammatory Markers, and Adipokines in Nondiabetic Patients with Metabolic Syndrome. Arterioscler Thromb Vasc Biol, 2006, 26(1): 182-188.
30.	Wang TD, Chen WJ, Lin JW, et al. Effects of Rosiglitazone on Endothelial Function, C-Reactive Protein, and Components of the Metabolic Syndrome in Nondiabetic Patients With th Metabolic Syndrome. Am J Cardiol, 2004, 93(3): 362-365.
31.	Wang TD, Chen WJ, Cheng WC, et al. Relation of Improvement in Endothelium-Dependent Flow-Mediated Vasodilation After Rosiglitazone to Changes in Asymmetric Dimethylarginine, Endothelin-1, and C-Reactive Protein in Nondiabetic Patients With the Metabolic Syndrome. Am J Cardiol, 2006, 98(8): 1057-1062.
32.	徐凤霞, 商宏伟, 李金华, 等. 罗格列酮对血糖正常的MS患者血管内皮功能和C反应蛋白的影响. 中国临床药理学杂志, 2005, 22(1): 15-17.
33.	Isomaa B, Almgren P, Tuonfi T, et a1. Cardiovascular morbidity and mortality associate with the metabolic syndrome. Diabetes Care, 2001, 24(4): 683-689.
34.	Lakka HM, laaksonen DE, Lakka TA, et a1. The metabolic syndrome and total and cardiovascular disease mortality in middle aged men. JAMA, 2002, 288(21): 2709-2716.
35.	Hunt KJ, Resendz RG, Williams K, et al. NCEP versus WHO metabolic syndrome in relation to all cause and cardiovascular mortality in the San Antonio Heart Study (SAHS) [abstract]. Diabetes, 2003, 52(1): A221-227.

1. responsiveness to its antidiabetic effect. Diabets Care, 2003, 26(9): 2493-2499.
2. Metabolic Syndrome Treated with Glimepiride: A Twelve-Month, Multicenter, Double-Blind, Randomized, Controlled, Parallel-Group Trial. Clinical Therapeutics, 2004, 26(5): 746-754.
3. Douglas JA, Erdos MR, Watanabe RM, et al. The Peroxisome Proliferator–Activated Receptor- 2 Pro12Ala Variant: Association With Type 2 Diabetes and Trait Differences. Diabetes, 2001, 50(4): 886- 890.
4. Viberti G, Kahn SE, Greene DA, et al. A Diabetes Outcome Progression Trial (ADOPT): An international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. Diabetes Care, 2002, 25(10): l737- l743.
5. MartensF M, VisserenF L, LemayJ, et al. Metabolic and additional vascular effects of thiazolidinediones. Drug, 2002, 62(10): 1463-1480.
6. 徐成斌. 代谢综合征. 国外医学内分泌学分册. 2005, 25(1): 3-6.
7. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trail. Lancet, 2005, 366(9493): 1279-1289.
8. Marx N & Hombach V. Peroxisome proliferator-activated receptors (PPARs) in the vessel wall: new regulators of gene expression in vascular cells (in German). Zeitschrift für Kardiologie, 2001, 90(7): 470-477.
9. Goetze S, XI XP, Kawano H, et al. PPAR gamma-ligands inhibit migration mediated by multiple chemoattractants in vascular smooth muscle cells. Journal of Cardiovascular Pharmacology, 1999, 33(5): 798-806.
10. Jiang C, Ting AT, Seed B. PPAR-agonists inhibit production of monocyte inflammatory cytokines. Nature, 1998, 391(6662): 82-86.
11. Chinetti G, Griglio S, Antonucci M, et al. Activation of proliferatoractivated receptors and induces apoptosis of human monocytederived macrophages. J Biol Chem, 1998, 273(40): 25573-25580.
12. Koshi y ama H, Shimono D, Kuwamur a N, et al . Rapid communication: inhibitory effect of pioglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab, 2001, 86(7): 3452-3456.
13. Satoh N, Ogawa Y, Usul T, et al. Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the.
14. Haffner SM, Greenberg AS, Weston WM, et al. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation, 2002, 106(6): 679-684.
15. Pfutzner A, Marx N, Lubben G, et al. Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the pioneer study. J Am Coll Cardiol, 2005, 45(12): 1925-1931.
16. Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care, 2005, 28(7): 1547-1554.
17. Fullert S, Schneider F, Haak E, et al. Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind, placebocontrolled study. J Clin Endocrinol Metab, 2002, 87(12): 5503-5506.
18. Raji A, Williams GH, Seely EW, et al. Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients. Diabetes Care, 2003, 26(1): 172-178.
19. Alberti KGMM, Zimmet PZ, WHO Consultation. Definition,diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med, 1998, 15(7): 539-553.
20. Expert Panel on Detection, Evaluation, and Treatment of High Blood cholesterol in Adults (Adult treatment Panel Ⅲ). Executive summary of the third report of the National Cholesteral Eduation Program (NECP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. J Am Med Assoc, 2001, 285(19): 2486-2497.
21. Barclay L. Medscape Medical News. New definition of the metabolic syndrome: a newsmaker interview with Sir George Alberti, MA, DPhil, BMBCh. Available at: http: //www. medscape. com/viewarticle/504382 Accessed July 8, 2005.
22. 吴泰相, 刘关键. 隐蔽分组（分配隐藏）和盲法的概念、实施与报告. 中国循证医学杂志, 2007, 7(3): 222-225.
23. Cao Z, Zhou YJ, Zhao YX, et al. Rosiglitazone could improve clinical outcome after coronary stent implantation in nondiabetes patients with metabolic syndrome. Chinese Medical Journal, 2006, 119(14): 1171-1175.
24. Samaha FF, Szapary PO, Iqbal N, et al. Effects of Rosiglitazone on Lipids, Adipokines, and Inflammatory Markers in Nondiabetic Patients With Low High-Density Lipoprotein Cholesterol and Metabolic Syndrome. Arterioscler Thromb Vasc Biol, 2006, 26(3): 624-630.
25. Derosa G, Cicero AFG, Gaddi A, et al. Metabolic Effects of Pioglitazone and Rosiglitazone in Patients with Diabetes and.
26. Derosa G, Gaddi AV, Ciccarelli L, et al. Long-term effect of glimepiride and rosiglitazone on non-conventional cardiovascular risk factors in metformin-treated patients affected by metabolic syndrome: a randomized, double-blind clinical trial. The journal of international medical resesarch, 2005, 33(3): 284-294.
27. Derosa G, D’Angelo A, Ragonesi PD, et al. Metformin–pioglitazone and metformin- rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndrome. Journal of Clinical Pharmacy and Therapeutics, 2006, 31(4): 375-383.
28. Esposito K, Ciotola M, Carleo D, et al. Effect of Rosiglitazone on Endothelial Function and Inflammatory Markers in Patients With the Metabolic Syndrome. Diabetes Care, 2006, 29(5): 1071-1076.
29. Szapary PO, Bloedon LT, Samaha FF, et al. Effects of Pioglitazone on Lipoproteins, Inflammatory Markers, and Adipokines in Nondiabetic Patients with Metabolic Syndrome. Arterioscler Thromb Vasc Biol, 2006, 26(1): 182-188.
30. Wang TD, Chen WJ, Lin JW, et al. Effects of Rosiglitazone on Endothelial Function, C-Reactive Protein, and Components of the Metabolic Syndrome in Nondiabetic Patients With th Metabolic Syndrome. Am J Cardiol, 2004, 93(3): 362-365.
31. Wang TD, Chen WJ, Cheng WC, et al. Relation of Improvement in Endothelium-Dependent Flow-Mediated Vasodilation After Rosiglitazone to Changes in Asymmetric Dimethylarginine, Endothelin-1, and C-Reactive Protein in Nondiabetic Patients With the Metabolic Syndrome. Am J Cardiol, 2006, 98(8): 1057-1062.
32. 徐凤霞, 商宏伟, 李金华, 等. 罗格列酮对血糖正常的MS患者血管内皮功能和C反应蛋白的影响. 中国临床药理学杂志, 2005, 22(1): 15-17.
33. Isomaa B, Almgren P, Tuonfi T, et a1. Cardiovascular morbidity and mortality associate with the metabolic syndrome. Diabetes Care, 2001, 24(4): 683-689.
34. Lakka HM, laaksonen DE, Lakka TA, et a1. The metabolic syndrome and total and cardiovascular disease mortality in middle aged men. JAMA, 2002, 288(21): 2709-2716.
35. Hunt KJ, Resendz RG, Williams K, et al. NCEP versus WHO metabolic syndrome in relation to all cause and cardiovascular mortality in the San Antonio Heart Study (SAHS) [abstract]. Diabetes, 2003, 52(1): A221-227.

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噻唑烷二酮类药物治疗代谢综合征的系统评价

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《中国循证医学杂志》

噻唑烷二酮类药物治疗代谢综合征的系统评价

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