23030 A 1 chieve Nabil K. El Naggar Pradana Soewondo Mohammad E. Khamseh Jian-Wen Chen Jihad Haddad 983408-413.

D I A B E T E S R E S E A R C H A N D C L I N I C A L P R A C T I C E 9 8 ( 2 0 1 2 ) 4 0 8 4 1 3 内 容 刊 载 在 Sciverse ScienceDirect Diabetes Research and Clinical Practice 杂 志 网 站 主 页 :www.elsevier.com/locate/diabres 23030 A 1 chieve Nabil K. El Naggar Pradana Soewondo b Mohammad E. Khamseh c Jian-Wen Chen d Jihad Haddad e a Hai Al JameaJeddah, Jeddah 21433, The Kingdom of Saudi Arabia b Jalan Diponegoro No. 71, Jakarta 10430, Indonesia c Firouzgar d Novo Nordisk International Operations A/S e Hamazeh 文 稿 信 息 摘 要 2012 8 29 2012 9 20 2012 9 24 关 键 词 : 30 2 目 的 :A 1 chieve 6323 2 30 BHI30OGLD 30 BIAsp30OGLD 方 法 :A 1 chieve 24 2BIAsp30 结 果 : BHI30SD0.56 0.25 IU/kg BIAsp30 0.57 0.25 U/kg240.62 0.28 U/kgBHI30BIAsp30 HbA 1c 9.1% [76 mmol/mol] 1.7% [18 mmol/mol] 1.6) p<0.001fpg PPGp<0.00124 / / 0.69 0.03 5.31 2.04 0.1% 0.1 3.3 kg 结 论 :2 BHI30BIAsp30 BIAsp30 Clinicaltrials.gov NCT00869908 前 言 / * N.K. El Naggar (+966) 505353650. nelnaggar@yahoo.com 0168-8227/$ 2012 Elsevier Ireland Ltd FPG PPG HbA 1c [1,2] [3] FPG PPG [4] BHI RCT2 请 引 用 本 文 的 原 始 出 处 :Switching from biphasic human insulin 30 to biphasic insulin aspart 30 in type 2 diabetes is associated with improved glycaemic control and a positive safety profile: Results from the A 1 chieve study. Diab Res Clin Pract 2012;98:408 413.

D I A B E T E S R E S E A R C H A N D C L I N I C A L P R A C T I C E 9 8 ( 2 0 1 2 ) 4 0 8 4 1 3 409 T2D30 BIAsp 30 NovoMix 30 PPG BHI 30 [5]BHI 30 BIAsp 30 55% 50% 24%RCT IMPROVE PRESEN NovoMix 30T BHI 30BIAsp 30 [ 6, 7 ] A 1 chieve BIAsp 30 Levemir NovoRapid [8] A 1 chieve 2 BHI 30 OGLD BIAsp 30 OGLD 材 料 与 方 法 A 1 chieve 24 2 BIAsp30 BHI 30BIAsp 30 A 1 chieve 2008 112011 3 /28 4 2BIAsp 30 6 1224HbA 1c FBG PPG24 QoL SADR 4 4 ADR12 24 AE24 / 12 244 HbA 1c FPG PPGADR AE SAE ADR 24 EQ-5D / /EQ-5D 0 100 100 BIAsp 30 60000 0.015% SADR t HbA 1c FPG PPG <100 40 86 [SD] 结 果 A 1 chieve 667266323 BHI 30 OGLDBIAsp 30 OGLD 9 9 1 1 5. 7 % 5 8 5 401 120163 ADR5332 EAS 5200 FPG PPG HbA 1c

410 D I A B E T E S R E S E A R C H A N D C L I N I C A L P R A C T I C E 9 8 ( 2 0 1 2 ) 4 0 8 4 1 3 表 1 由 双 时 相 人 胰 岛 素 30 改 为 双 时 相 门 冬 胰 岛 素 30 治 疗 患 者 的 基 线 特 征 / 6323 1191 2210 650 512 1634 % 3588 (56.9) 655 (55.0) 1442 (65.3) 340 (52.3) 219 (42.8) 899 (55.4) SD 55.4 (12.5) 57.5 (15.5) 54.8 (10.7) 56.3 (11.4) 57.1 (12.2) 53.2 (12.5) kg SD 74.0 (14.8) 68.8 (10.9) 70.1 (11.4) 66.6 (13.1) 77.8 (13.2) 84.9 (16.3) BMI kg/m 2 SD 27.3 (5.1) 25.0 (3.2) 26.1 (3.9) 25.5 (4.6) 29.2 (5.4) 31.1 (5.8) 2 SD 11.1 (6.6) 10.6 (6.6) 10.1 (5.3) 10.4 (7.7) 12.4 (7.7) 12.5 (6.9) SD 7.3 (5.4) 7.4 (5.9) 7.1 (4.4) 7.5 (6.6) 7.2 (6.2) 7.5 ( 5.3) SD 3.3 (3.3) 3.4 (3.2) 3.0 (2.6) 2.8 (3.1) 5.2 (5.2) 5.1 (4.7) HbA 1c % SD [mmol/mol] 9.1 (1.7)[76] 8.7 (2.1)[72] 9.1 (1.4)[76] 9.5 (1.9)[80] 9.0 (1.6)[75] 9.4 (1.8)[79] BMISD 图 1 总 体 人 群 和 各 地 区 HbA 1c 的 平 均 下 降 *p<0.001 1123 EAS /n=991 /BIAsp 30 n=148 BIAsp 30 6323 56.9% 55.4 11.1 3.3 BMI27.3 kg/m 2 74.0 kg 1 BMI 33.3% 36.9% 35.7% 6.1% 49.7% BHI 300.56 (0.25) IU/kg BIAsp 30 0.57 (0.25) U/kg24 0.62 (0.28) U/kg 89.5%BHI 30 2486.6% 84.6%BIAsp 30 4.5% 24BIAsp 308.8% 10.0% 24 BIAsp 30 BHI 30BIAsp 30HbA 1c [SD] 9.1% [76 mmol/mol]1.7% [18 mmol/mol] (1.6) p<0.001 1 BHI 30

D I A B E T E S R E S E A R C H A N D C L I N I C A L P R A C T I C E 9 8 ( 2 0 1 2 ) 4 0 8 4 1 3 411 图 2 总 体 人 群 和 各 地 区 FPG 的 平 均 下 降 *p<0.001 FPG: 空 腹 血 糖 表 2 总 体 人 群 和 各 地 区 早 餐 后 血 糖 的 下 降 2961 722 1009 239 198 / 724 PG mmol/l SD 14.2 (4.3) 12.9 (4.2) 15.1 (3.9) 14.7 (4.8) 14.1 (4.3) 14.3 (4.4) 24 9.9 (2.8) 9.1 (2.0) 10.8 (3.2) 10.3 (3.4) 10.2 (2.8) 9.2 (2.4) 4.3 (4.3) 3.8 (4.3) 4.4 (4.0) 4.3 (5.2) 3.9 (4.9) 5.0 (4.2) [P ] [<0.001] [<0.001] [<0.001] [<0.001] [<0.001] [<0.001] PGSD 373 6.9% HbA 1c <7% [53 mmol/mol] B I A s p 3 0 2 4 1 5 2 0 3 3. 6 % HbA 1c <7% [<53 mmol/mol] p<0.0001fpg 10.2 3.4 mmol/l3.0 3.5 mmol/l p<0.001 224 PPG 2 PPG 4.5 [4.2] mmol/l PPG 3.7 [3.7] mmol/l p<0.001 0.69 / / 0.03 / / 5.31 / / 2.04 / / 2243.5%335 1702.7%216 951.5%119 24 0.08%12 0.06% 0.04% 1042 1 6. 5 % 2 5 8 4 2 4 4248.0%838 0.1%SADR / 0.3%24 SAE 19 SAE 11 103

412 D I A B E T E S R E S E A R C H A N D C L I N I C A L P R A C T I C E 9 8 ( 2 0 1 2 ) 4 0 8 4 1 3 24 0.1 3.3 kg +0.5 kg 0 kg +0.6 kg +0.5 / 0.4 kg 0= 100= SD 64.0 16.376.5 11.9 BIAsp 30 91.4%35.3% 34.3%PG29.3% 26.0% 讨 论 BHI 30BIAsp 30HbA 1c FPG PPG SADR SAE 24 24 BIAsp 30 BHI 30 BIAsp 30 PPG RCT RCT BHI BIAsp 30 PPG[9-11] PPGBHI BIAsp 30 [12] PPG HbA 1c [1;2] PPG[3] PPG [4] PPG12.9 15.1 mmol/l IDFPPG <9 mmol/l [4] 24 BIAsp 30PPG4.3 mmol/l 9.9 mmol/l IDF BHI BIAsp 30 FPG[5;13] B I A s p 3 0 B H I HbA 1c [5;13;14] HbA 1c 1.2 1.9% A 1 chieve A 1 chieve HbA 1c [8] 24 BIAsp 30 BHI [5] 2007McNally BIAsp 30 BHI 30 [12] BIAsp 30 BHI 30 BHI 30 A 1 chieve 4 A 1 chieve / A 1 chieve A 1 chieve BHI 30BIAsp 30 BHI 30 2 BIAsp 30 BIAsp 30 SADR SAE 利 益 冲 突 El Naggar Soewondo Khamseh Haddad Haddad Chen

D I A B E T E S R E S E A R C H A N D C L I N I C A L P R A C T I C E 9 8 ( 2 0 1 2 ) 4 0 8 4 1 3 413 致 谢 A 1 chieve Chundo Shen Watermeadow Medical Michael Lappin 研 究 资 金 支 持 参 考 文 献 A 1 chieve [1] Monnier L, Colette C. Targeting prandial hyperglycemia: how important is it and how best to do this? Curr. Diab. Rep., 2008;8:368-74. [2] Woerle HJ, Neumann C, Zschau S, Tenner S, Irsigler A, Schirra J, et al. Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes Importance of postprandial glycemia to achieve target HbA 1c levels. Diabetes Res. Clin. Pract., 2007;77(2):280-5. [3] Ceriello A, Davidson J, Hanefeld M, Leiter L, Monnier L, Owens D, et al. Postprandial hyperglycaemia and cardiovascular complications of diabetes: an update. Nutr. Metab. Cardiovasc. Dis., 2006;16:453-6. [4] International Diabetes Federation. Guideline For Management Of Postmeal Glucose In Diabetes 2011. International Diabetes Federation 2012. Accessed: August 22. Available from: URL: http://www.idf. org/2011-guidelinemanagement-postmeal-glucosediabetes [5] Davidson JA, Liebl A, Christiansen JS, Fulcher G, Ligthelm RJ, Brown P, et al. Risk for nocturnal hypoglycemia with biphasic insulin aspart 30 compared with biphasic human insulin 30 in adults with type 2 diabetes mellitus: a metaanalysis. Clin. Ther., 2009;31:1641-51. [6] Shah S, Benroubi M, Borzi V, Gumprecht J, Kawamori R, Shaban J, et al. Safety and effectiveness of biphasic insulin aspart 30/70 (NovoMix 30) when switching from human premix insulin in patients with type 2 diabetes: subgroup analysis from the 6-month IMPROVE observational study. Int. J. Clin. Pract. 2009;63:574-82. [7] Shestakova M, Sharma SK, Almustafa M, Min KW, Ayad N, Azar ST, et al. Transferring type 2 diabetes patients with uncontrolled glycaemia from biphasic human insulin to biphasic insulin aspart 30: experiences from the PRESENT study. Curr. Med. Res. Opin., 2007;23:3209-14. [8] Home P, Naggar NE, Khamseh M, Gonzalez-Galvez G, Shen C, Chakkarwar P, et al. An observational noninterventional study of people with diabetes beginning or changed to insulin analogue therapy in non-western countries: the A 1 chieve study. Diabetes Res. Clin. Pract., 2011;94:352-63. [9] McSorley PT, Bell PM, Jacobsen LV, Kristensen A, Lindholm A. Twice-daily biphasic insulin aspart 30 versus biphasic human insulin 30: a doubleblind crossover study in adults with type 2 diabetes mellitus. Clin. Ther., 2002;24:530-9. [10] Boehm BO, Home PD, Behrend C, Kamp NM, Lindholm A. Premixed insulin aspart 30 vs. premixed human insulin 30/70 twice daily: a randomized trial in Type 1 and Type 2 diabetic patients. Diabet. Med., 2002;19:393-9. [11] Hermansen K, Colombo M, Storgaard H, OStergaard A, Kolendorf K, Madsbad S. Improved postprandial glycemic control with biphasic insulin aspart relative to biphasic insulin lispro and biphasic human insulin in patients with type 2 diabetes. Diabetes Care, 2002;25:883-8. [12] McNally PG, Dean JD, Morris AD, Wilkinson PD, Compion G, Heller SR. Using continuous glucose monitoring to measure the frequency of low glucose values when using biphasic insulin aspart 30 compared with biphasic human insulin 30: a double-blind crossover study in individuals with type 2 diabetes. Diabetes Care, 2007;30:1044-8. [13] Qayyum R, Wilson LM, Bolen S, Maruthur N, Marinopoulos SS, Feldman L, et al. Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults With Type 2 Diabetes. Rockville (MD): Agency for Healthcare Research and Quality (US). Available from: http://www. ncbi.nlm.nih.gov/books/nbk43174/. [14] Boehm BO, Vaz JA, Brondsted L, Home PD. Long-term efficacy and safety of biphasic insulin aspart in patients with type 2 diabetes. Eur. J. Intern. Med., 2004;15:496-502.