The NEW ENGLAND JOURNAL f MEDICINE 2 名合超罗吕贷 分三黄日登生尽密昌云台名8 美喜 合云日的宝 华日吕的高司9为空会3名曾品的 pue 雕H N ENGLJ MED 356:24 WWW.NEJM.ORG JUNE 14.2007 use only
T h e n e w e ng l a nd j o u r na l o f m e dic i n e 2460 n engl j med 356;24 www.nejm.org june 14 , 2007 Table 1. Clinical Trials of Rosiglitazone in the Meta-Analysis.* Study and Reference Registry Number Phase Duration Rosiglitazone Group Control Group Drug No. of Patients Drug No. of Patients wk Trials included in original registration package 49653/0115-7 3 24 Rosiglitazone 357 Placebo 176 49653/0205,6 3 52 Rosiglitazone 391 Glyburide 207 49653/0245,6,8 3 26 Rosiglitazone 774 Placebo 185 49653/0935,6,9 3 26 Rosiglitazone with or without metformin 213 Metformin 109 49653/0945,6,9,10 3 26 Rosiglitazone and metformin 232 Metformin 116 Subtotal 1,967 793 Additional phase 2, 3, and 4 efficacy trials 1006845 4 52 Rosiglitazone and glyburide 43 Glyburide 47 49653/1435 4 24 Rosiglitazone and glyburide 121 Glyburide 124 49653/2115 4 52 Rosiglitazone and usual care 110 Usual care 114 49653/2845,11 4 24 Rosiglitazone and metformin 382 Metformin 384 712753/0085 4 48 Rosiglitazone and metformin 284 Metformin 135 AVM1002645 NCT00359112 4 52 Rosiglitazone and metformin 294 Metformin and sulfonylurea† 302 BRL 49653C/1855 4 32 Rosiglitazone with or without metformin 563 Usual care with or without metformin 142 BRL 49653/3345 4 52 Rosiglitazone 278 Placebo 279 BRL 49653/3475 NCT00054782 4 24 Rosiglitazone and insulin 418 Insulin 212 49653/0155,12 3 24 Rosiglitazone and sulfonylurea‡ 395 Sulfonylurea‡ 198 49653/0795 3 26 Rosiglitazone with or without glyburide 203 Glyburide 106 49653/0805,13 3 156 Rosiglitazone 104 Glyburide 99 49653/0825,14 3 26 Rosiglitazone and insulin 212 Insulin 107 49653/0855 3 26 Rosiglitazone and insulin 138 Insulin 139 49653/0955 3 26 Rosiglitazone and insulin 196 Insulin 96 49653/0975 3 156 Rosiglitazone 122 Glyburide 120 The New England Journal of Medicine Downloaded from nejm.org on February 5, 2016. For personal use only. No other uses without permission. Copyright © 2007 Massachusetts Medical Society. All rights reserved
ROSIGLITAZONE AND CARDIOVASCULAR OUTCOMES 图网网闲目生常赠型可的8超用尉五多目百景 及剑 a能服：用 投品份质吕生有8超吕耳发月用日月当羊香 月堂屋 ap/z N ENGLJ MED 356;24 WWW.NEJM.ORG JUNE 14,2007 246 The New England Joumal of Medicine
Rosiglitazone and Cardiovascular Outcomes n engl j med 356;24 www.nejm.org june 14 , 2007 2461 49653/1255,15 3 26 Rosiglitazone and sulfonylurea§ 175 Sulfonylurea§ 173 49653/1275 3 26 Rosiglitazone and glyburide 56 Glyburide 58 49653/1285 3 28 Rosiglitazone 39 Placebo 38 49653/1345 3 28 Rosiglitazone 561 Placebo 276 49653/1355 3 104 Rosiglitazone and glipizide 116 Glipizide 111 49653/1365 3 26 Rosiglitazone 148 Placebo 143 49653/1455,16 3 26 Rosiglitazone and gliclazide 231 Gliclazide 242 49653/1475,17 3 26 Rosiglitazone and sufonylurea¶ 89 Sulfonylurea¶ 88 49653/1625,18 3 26 Rosiglitazone and glyburide 168 Glyburide 172 49653/2345 3 26 Rosiglitazone and glimepiride 116 Glimepiride 61 49653/3305 3 52 Rosiglitazone 1,181 Placebo 382 49653/3315 3 52 Rosiglitazone 706 Placebo 325 49653/1375 3 32 Rosiglitazone and metformin 204 Glyburide and metformin 185 SB-712753/0025 3 24 Rosiglitazone and metformin 288 Metformin 280 SB-712753/0035 3 32 Rosiglitazone and metformin 254 Metformin 272 SB-712753/0075 3 32 Rosiglitazone with or without metformin 314 Metformin 154 SB-712753/0095 3 24 Rosiglitazone, metformin, and insulin 162 Insulin 160 49653/1325,19 2 24 Rosiglitazone and sulfonylurea‖ 442 Sulfonylurea‖ 112 AVA1001935 2 24 Rosiglitazone 394 Placebo 124 Subtotal 9,507 5,960 Recently published large, prospective, randomized trials DREAM20 NCT00095654 3 156 Rosiglitazone 2,635 Placebo 2,634 ADOPT21 NCT00279045 3 208 Rosiglitazone 1,456 Metformin or glyburide 2,895 Total 15,565 12,282 * Studies are listed according to the number designated by the sponsor, GlaxoSmithKline, and are available on the company’s Web site.5 ClinicalTrials.gov numbers are listed for trials included in that registry. DREAM denotes Diabetes Reduction Assessment with Ramipiril and Rosiglitazone Medication, and ADOPT A Diabetes Outcome Prevention Trial. † The administered drug was either glyburide or gliclazide. ‡ The administered drug was glyburide, gliclazide, or glipizide. § The administered drug was glyburide, glipizide, gliclazide, chlorpropamide, glimepiride, or tolbutamide. ¶The type of sulfonylurea was unspecified. ‖ The administered drug was glyburide, glipizide, gliclazide, chlorpropamide, gliquidone, or tolbutamide. The New England Journal of Medicine Downloaded from nejm.org on February 5, 2016. For personal use only. No other uses without permission. Copyright © 2007 Massachusetts Medical Society. All rights reserved
The NEW ENGLAND JOURNAL f MEDICINE 芝登88F的6芝受芝品号8g886888888 日总母甲云日品88日府日88员8学草8年8常8供88 是生氏片兴只居8日品烘员日份日品员88后8日日份含品98吕君 2a-0002An pe -1002um O-00z 866T yW-966t ny pue 'Apnis'sns 目皇皇道2酯：经经 246 N ENGLJ MED 356:24 WWW.NEJM.ORG JUNE 14.2007
T h e n e w e ng l a nd j o u r na l o f m e dic i n e 2462 n engl j med 356;24 www.nejm.org june 14 , 2007 Table 2. Doses, Baseline Demographic Characteristics, Study Periods, and Glycated Hemoglobin Levels.* Study Drug Daily Dose Population Study Period Age Male Sex Race† Baseline Glycated Hemoglobin Level yr percent 100684 Rsg/Gly 4 or 8 mg Korean patients with type 2 DM Dec. 2003–July 2005 55.2 53.5 100 A NA Gly 5–15 mg 54.5 45.6 100 A NA 49653/143 Rsg/Gly 8 mg Type 2 DM poorly controlled on glyburide July 2000– Jan. 2003 52 45.3 44:56 B:H 9.2 Gly Usual care 53 48.3 38:62 B:H 9.4 49653/211 Rsg 4 mg Type 2 DM with CHF July 2001–Nov. 2003 64.3 84.3 99 7.7 Plc — 63.9 79.0 99 7.8 49653/284 Rsg/Met 4 or 8 mg/1 g Type 2 DM June 2001–Feb. 2003 55.5 51.1 72 8.1 Met 1–2 g 55.6 51.0 71 7.9 712753/008 Rsg/Met 8 mg/1 g Type 2 DM poorly controlled on Met June 2003–Dec. 2005 54.6 63.2 70 NA Rsg/Met 4 mg/2 g 56.0 65.2 78 NA Met 2g 56.9 53.4 69 NA AVM100264 Rsg/Met 4 or 8 mg/2 g Overweight patients with type 2 DM poorly controlled on Met July 2004–Jan. 2006 58.5 52.7 94 8.0 Met/Su 2 g/titrated 59.3 52.5 95 8.0 BRL49653C/185 Rsg/ELM/Met 4 mg/1.5 g Type 2 DM May 2000–May 2002 58.0 65.2 76 7.5 Rsg/ELM 4 mg 59.0 60.2 78 7.4 Met/ELM 1.5 g 60.0 56.4 78 7.5 ELM — 57.0 60.9 83 7.4 BRL 49653/334 Rsg 4 or 8 mg Type 2 DM or insulin resistance syndrome March 2002–Nov. 2004 67.7 44.8 99 6.3 Plc — 67.3 47.7 100 6.3 BRL 49653/347 Rsg/insulin 4 mg Type 2 DM poorly controlled on insulin Nov. 2002–April 2004 52.6 48.1 57 9.0 Rsg/insulin 2 or 4 mg 52.7 60.0 57 8.9 Insulin/Plc Usual care 53.8 46.2 57 9.1 49653/011 Rsg 8 mg Type 2 DM Sept. 1996–Sept. 1997 60.7 66.9 73 8.8 Rsg 4 mg 59.6 64.5 75 9.0 Plc — 58.8 65.8 74 9.0 49653/015 Rsg/Su 4 mg Type 2 DM Aug. 1996–March 1998 60.6 53.2 98 9.2 Rsg/Su 2 mg 61.0 62.8 86 9.2 Su 61.9 57.3 97 9.2 The New England Journal of Medicine Downloaded from nejm.org on February 5, 2016. For personal use only. No other uses without permission. Copyright © 2007 Massachusetts Medical Society. All rights reserved
ROSIGLITAZONE AND CARDIOVASCULAR OUTCOMES 然房0品88品6gg8863芝芝388886附688云86品 公8ge的品天RRR8R9不88昌曾8品品云R8R品日昏R 份8食品厨8会88著日食牙品供牙学8份88冠发器后导发每月品 888日贷段没6云6发因员66日君甘因关安日贯谷的母份虽发日8厨 員国 掌 dy-266t ounf 3nV-6661 壁整合墨望壁望是 事a:复复1是室市 昌昌香昌 N ENGLJ MED 356;24 WWW.NEJM.ORG JUNE 14,2007 246 The New England Joumal of Medicine
Rosiglitazone and Cardiovascular Outcomes n engl j med 356;24 www.nejm.org june 14, 2007 2463 49653/020 Rsg 8 mg Type 2 DM Oct. 1996–May 1998 60.9 57.6 97 8.2 Rsg 4 mg 60.4 68.2 99 8.1 Gly Titrated 60.1 70.4 99 8.2 49653/024 Rsg 4 mg once daily Type 2 DM Jan. 1997–Feb. 1998 57.5 58.6 76 8.9 Rsg 2 mg twice daily 56.8 59.1 78 8.9 Rsg 8 mg once daily 58.9 65.7 80 8.9 Rsg 4 mg twice daily 56.5 59.9 71 9.0 Plc — 57.7 68.8 79 8.9 49653/079 Rsg 4 mg Type 2 DM poorly controlled on maximum dose of Gly April 1997–March 1998 59.1 63.6 70 9.1 Rsg/Gly 4 mg/20 mg 57.7 69.4 70 9.2 Gly 20 mg 58.5 66.7 69 9.3 49653/080 Rsg 8 mg Type 2 DM Nov. 1996–May 2000 55.1 75.0 73 8.9 Gly 2.5–5.0 mg 56.1 70.1 76 9.4 49653/082 Rsg/insulin 8 mg Type 2 DM poorly controlled on insulin July 1997–Aug. 1998 57.7 54.3 71 9.0 Rsg/insulin 4 mg 57.1 56.6 72 9.1 Insulin Usual care 55.6 55.8 68 8.9 49653/085 Rsg/insulin 4 or 8 mg Type 2 DM May 2000–June 2001 61.3 54.0 99 NA Insulin Usual care 61.5 46.8 100 NA 49653/093 Rsg/Met 8 mg/2.5 g Type 2 DM poorly controlled on Met June 1997–April 1998 57.8 60.0 58 8.7 Rsg 8 mg 58.8 53.7 59 8.7 Met 2.5 g 59.5 67.0 60 8.8 49653/094 Rsg/Met 8 mg/2.5 g Type 2 DM poorly controlled on Met April 1997–March 1998 58.3 68.2 77 8.9 Rsg/Met 4 mg/2.5 g 57.5 62.1 80 8.9 Met 2.5 g 58.8 74.3 81 8.6 49653/095 Rsg/insulin 8 mg Type 2 DM poorly controlled on insulin Aug. 1997–Dec. 1998 57.4 58.9 73 9.1 Rsg/insulin 4 mg 57.8 63.9 68 8.8 Insulin Usual care 58.9 45.3 73 9.1 49653/097 Rsg 8 mg Type 2 DM Aug. 1997–Jan. 2001 55.8 72.1 74 8.9 Gly Titrated 56.0 70.8 84 8.8 49653/125 Rsg/Su 4 mg Type 2 DM May 1999–Aug. 2000 54.6 45.7 56 A 9.1 Su Usual care 57.3 42.4 59 A 8.9 49653/127 Rsg/Gly 8 mg/<20 mg Type 2 DM poorly controlled on Gly Jan. 1999–Dec. 1999 60.0 51.0 75 9.1 Gly <20 mg 59.4 66.0 75 8.9 The New England Journal of Medicine Downloaded from nejm.org on February 5, 2016. For personal use only. No other uses without permission. Copyright © 2007 Massachusetts Medical Society. All rights reserved
The NEW ENGLAND JOURNAL f MEDICINE 886号9的的8的888e品西的芝芝受乏N 复盈豆天8尺保云8聚公家自自公8昌金含8示8888 日型8员8天88日8月网日君导888888庆份 曼红然6日日因g8石品生8贯8g8等导￥毁日 zn-6661n 00200000 us-opu E买 复是a屋a多65发兰￥盖 8 N ENGLJ MED 356:24 WWW.NEJM.ORG JUNE 14.2007
T h e n e w e ng l a nd j o u r na l o f m e dic i n e 2464 n engl j med 356;24 www.nejm.org june 14 , 2007 Table 2. (Continued.) Study Drug Dose Population Study Period Age Male Sex Race† Baseline Glycated Hemoglobin Level yr percent 49653/128 Rsg/Su 4 mg Type 2 DM on concurrent Su May 1999–June 2000 58.3 51.3 100 A 9.6 Su Usual care 57.7 42.1 100 A 9.9 49653/134 Rsg/Gly/Met 8 mg Type 2 DM on Gly and Met March 1999– Aug. 2000 55.5 62.0 71 8.7 Rsg/Gly/Met 4 mg 55.6 58.0 68 8.6 Gly/Met Usual care 55.8 61.0 71 8.7 49653/135 Rsg/Glip 4 or 8 mg/ 20–40 mg Elderly patients with type 2 DM May 1999– Oct. 2002 68.7 74.1 90 7.6 Glip 20–40 mg 68.2 71.2 91 7.3 49653/136 Rsg/Su/insulin 4 or 8 mg Type 2 DM with chronic renal failure on Su, insulin, or both July 1999–June 2001 64.9 60.7 97 8.2 Su/insulin Usual care 66.3 60.8 98 8.3 49653/145 Rsg/Su 8 mg Type 2 DM Oct. 1999–Nov. 2000 61.1 57.3 97 8.5 Su Usual care 61.9 62.7 98 8.6 49653/147 Rsg/Su 8 mg Indo-Asian patients with type 2 DM July 1999–Aug. 2000 54.3 20.2 100 A 9.2 Su Usual care 54.1 25.3 100 A 9.1 49653/162 Rsg/Gly 8 mg Type 2 DM Nov. 2000–April 2002 60.0 55.1 97 7.9 Gly Maximum, 15 mg 59.9 61.8 96 8.0 49653/234 Rsg/Glim 8 mg Type 2 DM Jan. 2001–Feb. 2002 62.9 44.0 100 8.1 Rsg/Glim 4 mg 60.5 57.0 100 8.2 Glim Up-titrated 65.0 60.0 100 7.9 49653/330 Rsg 8 mg Chronic psoriasis Jan. 2003–Oct. 2004 44.3 65.0 92 NA Rsg 4 mg 44.8 66.0 91 NA Rsg 2 mg 45.0 63.0 90 NA Plc — 44.5 63.0 93 NA SB-712753/003 Rsg/Met 4 or 8 mg/1–3 g Mild type 2 DM June 2003–Dec. 2004 58.9 54.7 98 7.2 Met 1–3 g 59.0 55.5 99 7.2 The New England Journal of Medicine Downloaded from nejm.org on February 5, 2016. For personal use only. No other uses without permission. Copyright © 2007 Massachusetts Medical Society. All rights reserved