參考資料 - 易週糖注射劑

1. Scheen AJ. Pathophysiology of type 2 diabetes. Acta Clinica Belgica 2003;

58(6).

2. DeFronzo RA. From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus. Diabetes 2009; 58(4): 773-795.

3. 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. Diabetes Care 2015; 38(1): 140-149.

4. Global Guideline for Type 2 Diabetes. International Diabetes Federation.

http://www.idf.org/sites/default/files/IDF-Guideline-for-Type-2-Diabetes.pdf.

Published 2012. Accessed October 21, 2015.

5. 社團法人中華民國糖尿病學會. 2015 糖尿病臨床照護指引; 2015 年 3 月.

6. 仿單：易週糖^®注射劑 1.5 毫克/0.5 毫升、0.75 毫克/0.5 毫升. 台灣禮來

股份有限公司 .

http://www.fda.gov.tw/MLMS/ShowFile.aspx?LicId=60000979&Seq=001&T ype=9. Accessed October 21, 2015.

7. ATC/DDD Index 2015. WHO Collaborating Centre for Drug Statistics Methodology Norwegian Institute of Public Health.

http://www.whocc.no/atc_ddd_index/. Accessed October 21, 2015.

8. 藥物、醫療器材、含化妝品許可證查詢作業. 衛生福利部食品藥物管理署.

http://www.fda.gov.tw/MLMS/(S(f1m5sqyryjtvctupbwqvin45))/H0001.aspx.

Accessed October 21, 2015.

9. 健保用藥品項查詢 . 衛生福利部中央健康保險署 .

http://www.nhi.gov.tw/query/query1.aspx?menu=21&menu_id=713&webdata _id=3510&WD_ID=851. Accessed October 21, 2015.

10. 藥品給付規定內容(最新版)：第五節激素及影響內分泌機轉藥物. 衛生福

利部中央健康保險署 .

http://www.nhi.gov.tw/02hospital/hospital_file/chap5.doc. Accessed October

21, 2015.

11. Drug Product Database Online Query. Health Canada.

http://webprod5.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp. Accessed October 21,

2015.

12. CADTH Homepage. Canadian Agency for Drugs and Technologies in Health.

https://www.cadth.ca/. Accessed October 21, 2015.

13. Search the ARTG. Therapeutic Goods Administration.

https://www.tga.gov.au/search/artg. Accessed October 21, 2015.

14. Department of Health: Homepage. Commonwealth of Australia.

http://www.health.gov.au/. Accessed October 21, 2015.

15. Pharmaceutical Benefits Advisory Committee (PBAC). Pharmaceutical Benefits Scheme. http://www.pbs.gov.au/info/industry/listing/participants/pbac.

Accessed October 21, 2015.

16. Pharmaceutical Benefits Scheme (PBS) : Homepage. Pharmaceutical Benefits Scheme. http://www.pbs.gov.au/pbs/home. Accessed October 21, 2015.

17. NICE advice [ESNM59]: Type 2 diabetes: dulaglutide. National Institute for

Health and Care Excellence.

https://www.nice.org.uk/advice/esnm59/chapter/Full-evidence-summary.

Published June 2015. Accessed October 21, 2015.

18. Forthcoming Submission: dulaglutide (Trulicity). Scottish Medicines Consortium.

https://www.scottishmedicines.org.uk/SMC_Advice/Forthcoming_Submission

s/dulaglutide_Trulicity. Accessed October 21, 2015.

19. Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care 2014; 37(8):

2159-2167.

20. Giorgino F, Benroubi M, Sun JH, Zimmermann AG, Pechtner V. Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride (AWARD-2). Diabetes Care 2015.

21. Umpierrez G, Povedano ST, Manghi FP, Shurzinske L, Pechtner V. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care 2014; 37(8):

2168-2176.

22. Blonde L, Jendle J, Gross J, et al. Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): A randomised, open-label, phase 3, non-inferiority study. The Lancet 2015; 385(9982): 2057-2066.

23. Nauck M, Weinstock RS, Umpierrez GE, Guerci B, Skrivanek Z, Milicevic Z.

Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care 2014;

37(8): 2149-2158.

24. Weinstock RS, Guerci B, Umpierrez G, Nauck MA, Skrivanek Z, Milicevic Z.

Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2years

phase III study. Diabetes, Obesity and Metabolism 2015; 17(9): 849-858.

25. Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. Lancet (London, England) 2014; 384(9951): 1349-1357.

26. Araki E, Inagaki N, Tanizawa Y, Oura T, Takeuchi M, Imaoka T. Efficacy and safety of once-weekly dulaglutide in combination with sulphonylurea and/or biguanide compared with once-daily insulin glargine in Japanese patients with type 2 diabetes: A randomized, open-label, phase III, non-inferiority study.

Diabetes, Obesity and Metabolism 2015; 17(10): 994-1002.

27. Miyagawa J, Odawara M, Takamura T, Iwamoto N, Takita Y, Imaoka T.

Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once-daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: A 26-week randomized phase III study. Diabetes, Obesity and Metabolism 2015; 17(10): 974-983.

28. A Study in Participants With Type 2 Diabetes Mellitus (AWARD-1).

ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT01064687.

Accessed October 21, 2015.

29. A Study in Participants With Type 2 Diabetes Mellitus (AWARD-2).

ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/study/NCT01075282.

Accessed October 21, 2015.

30. A Study in Participants With Type 2 Diabetes Mellitus (AWARD-3).

ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT01126580.

Accessed October 21, 2015.

31. A Study in Participants With Type 2 Diabetes Mellitus (AWARD-4).

ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/study/NCT01191268.

Accessed October 21, 2015.

32. A Study of LY2189265 Compared to Sitagliptin in Participants With Type 2 Diabetes Mellitus on Metformin. ClinicalTrials.gov.

https://clinicaltrials.gov/ct2/show/NCT00734474. Accessed October 21, 2015.

33. Skrivanek Z, Gaydos BL, Chien JY, et al. Dose-finding results in an adaptive, seamless, randomized trial of once-weekly dulaglutide combined with metformin in type 2 diabetes patients (AWARD-5). Journal 2014; 16(8):

748-756. DOI: 10.1111/dom.12305. Available from:

http://onlinelibrary.wiley.com/store/10.1111/dom.12305/asset/dom12305.pdf?

v=1&t=ig1j38hq&s=2c1c747524c7cc718b2cd7216e878e41fac12ce4.

34. A Study Comparing the Effect of Dulaglutide With Liraglutide in Type 2 Diabetes (AWARD-6). ClinicalTrials.gov.

https://clinicaltrials.gov/ct2/show/NCT01624259. Accessed October 21, 2015.

35. A Study of Dulaglutide in Japanese Participants With Type 2 Diabetes Mellitus.

ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01584232. Accessed October 21, 2015.

36. A Study of LY2189265 in Japanese Participants With Type 2 Diabetes Mellitus.

ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01558271. Accessed October 21, 2015.

37. Charokopou M, Chuang L, Verheggen B, Gibson D, Grandy S, Kartman B.

Cost-Effectiveness Analysis of Exenatide Once-Weekly Versus Dulaglutide, Liraglutide and Lixisenatide for the Treatment of Type 2 Diabetes Mellitus: An Analysis from the UK NHS Perspective. Value in health: the journal of the International Society for Pharmacoeconomics and Outcomes Research 2015;

18(7): A606.

38. Raibouaa A, Borgeke H, Alexiou D, Lowin J, Norrbacka K.

Cost-Effectiveness of Dulaglutide 1.5 mg Once Weekly for the Treatment of Patients with Type Two Diabetes Mellitus in Sweden. Value in health: the journal of the International Society for Pharmacoeconomics and Outcomes Research 2015; 18(7): A607.

附錄

附錄一文獻資料庫搜尋策略與結果

1. PubMed 電子文獻資料庫過程與結果（2015 年 10 月 21 日）

Search Query Items found

#1 dulaglutide 66

#2 ("dulaglutide"[Supplementary Concept] OR "dulaglutide"[All Fields]) AND Randomized Controlled Trial[ptyp]

2. Embase 電子文獻資料庫過程與結果（2015 年 10 月 21 日）

Search Query Items found

#1 'dulaglutide'/exp OR dulaglutide 270

#2 'dulaglutide'/exp OR dulaglutide AND [randomized controlled trial]/lim 21 3. Cochrane Library 文獻資料庫搜尋策略與結果（2015 年 10 月 21 日）

No. Query Results

#1 dulaglutide:ti,ab,kw (Word variations have been searched)

Cochrane Database of Systematic

Reviews : Issue 9 of 12, September 2015 0

Cochrane Central Register of Controlled Trials : Issue 9 of 12, September 2015

附錄二系統性文獻搜尋排除之論文

第一作者年代標題排除原因

Reaney, M. 2014 Patient-reported outcomes (PRO) from a 104 week, phase 3, randomised, placebo-controlled study comparing once weekly dulaglutide to sitagliptin and placebo in metformin-treated patients with Type 2 diabetes; the Assessment of Weekly Administration of Dulaglutide in Diabetes (AWARD-5) trial

研討會摘要

Adetunji, O. 2014 A post-hoc pooled analysis of two placebo controlled phase 3 trials, Assessment of Weekly AdministRation of LY2189265 in Diabetes-1 and-5 (AWARD-1 and AWARD-5): Dulaglutide compared with exenatide, sitagliptin, and placebo

研討會摘要

Skrivanek, Z. 2013 Dose-finding results in an adaptive trial of dulaglutide combined with metformin in type 2 diabetes (AWARD-5)

研討會摘要 Guerci, B. 2013 Safety and efficacy of dulaglutide vs sitagliptin after 104 weeks in type 2 diabetes (AWARD-5) 研討會摘要 Wysham, C. 2013 Efficacy and safety of dulaglutide versus placebo and exenatide in type 2 diabetes (AWARD-1) 研討會摘要 Giorgino, F. 2014 Efficacy and safety of once weekly dulaglutide vs insulin glargine in combination with metformin and

glimepiride in type 2 diabetes patients (AWARD-2)

研討會摘要

Forst, T. 2014 The 2 week fasting glucose as a predictor of response to once weekly dulaglutide 1.5 mg 評估以 fasting glucose 來預測治療效果。PICOS 不符合。

Jendle, J. 2014 Better glycaemic control and less weight gain with once weekly dulaglutide vs bedtime insulin glargine, both combined with thrice daily lispro, in type 2 diabetes (AWARD-4)

研討會摘要 Nauck, M. A. 2013 Efficacy and safety of dulaglutide vs sitagliptin after 52 weeks in type 2 diabetes (AWARD5) 研討會摘要 Reaney, M. 2014 Patient-reported outcomes with once-weekly dulaglutide vs. Insulin glargine, both in combination with

premeal insulin lispro, in type 2 diabetes mellitus (AWARD-4)

研討會摘要 Nauck, M. 2013 Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes (award-5) 研討會摘要 Tofe

Povedano, S.

2014 Efficacy and safety of once weekly dulaglutide versus once daily liraglutide in type 2 diabetes (AWARD6)

研討會摘要 Tofe 2013 Efficacy and safety of dulaglutide vs metformin in type 2 diabetes (AWARD-3) 研討會摘要

第一作者年代標題排除原因 Povedano, S.

Grunberger, G. 2011 Monotherapy with the once weekly long-acting GLP-1 analog LY2189265 for 12 weeks in patients with type 2 diabetes: Dose-dependent effects on glycemic control in a randomized, double-blind,

placebo-controlled study

研討會摘要

Grunberger, G. 2011 Monotherapy with the once-weekly GLP-1 analogue LY2189265 for 12 weeks in patients with type 2 diabetes: Dose-dependent effects in a randomised, double-blind, placebo-controlled study

研討會摘要 Dungan, K. M. 2014 Erratum: Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type

2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial (Lancet (2014) 384 (1349-1357))

勘誤說明。

Wysham, C. 2014 Erratum: Efficacy and Safety of Dulaglutide Added Onto Pioglitazone and Metformin Versus Exenatide in Type 2 Diabetes in a Randomized Controlled Trial(AWARD-1). (Diabetes Care 2014; 37

(2159-2167))

勘誤說明。

Reaney, M. 2015 Treatment satisfaction in people with type 2 diabetes mellitus treated with once-weekly dulaglutide: Data from the AWARD-1 and AWARD-3 clinical trials

合併 AWARD-1 和 AWARD-3 研究比較 dulaglutide 與

exenatide、placebo、或 metformin 的滿意度 Saulsberry,

W.J.

2015 Comparative efficacy and safety of antidiabetic drug regimens added to stable and inadequate metformin and thiazolidinedione therapy in type 2 diabetes

系統性文獻回顧暨統合分析研究。

Padhiar, A. 2014 A network meta-analysis to compare once weekly dulaglutide versus other GLP-1 receptor agonists in patients with type 2 diabetes

研討會摘要 Terauchi, Y. 2014 Monotherapy with the once weekly GLP-1 receptor agonist dulaglutide for 12 weeks in Japanese patients

with type 2 diabetes: Dose-dependent effects on glycaemic control in a randomised, Double-blind, Placebo-controlled study

劑量相關性之第二期臨床試驗。

Skrivanek, Z. 2014 Dose-finding results in an adaptive, seamless, randomized trial of once-weekly dulaglutide combined 僅針對第二期臨床試驗

第一作者年代標題排除原因

with metformin in type 2 diabetes patients (AWARD-5) 的部分說明。

Grunberger, G. 2012 Monotherapy with the once-weekly GLP-1 analogue dulaglutide for 12weeks in patients with Type2 diabetes: Dose-dependent effects on glycaemic control in a randomized, double-blind,

placebo-controlled study

劑量相關性之第二期臨床試驗。

Geiger, M.J. 2012 An adaptive, dose-finding, seamless phase 2/3 study of a long-acting glucagon-like peptide-1 analog (dulaglutide): Trial design and baseline characteristics

說明 AWARD-5 試驗的研究設計和方法學。

Skrivanek, Z. 2012 Application of adaptive design methodology in development of a long-acting glucagon-like peptide-1 analog (dulaglutide): Statistical design and simulations

說明 AWARD-5 試驗的統計分析方法學。

Umpierrez, G.E.

2011 The effects of LY2189265, a long-acting glucagon-like peptide-1 analogue, in a randomized, placebo-controlled, double-blind study of overweight/obese patients with type 2 diabetes: The EGO study

調整或固定劑量比較之第二期臨床試驗。

Barrington, P. 2011 A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analogue, in patients with type 2 diabetes

為藥物動力學和藥效動力學指標，非臨床指標。

Barrington, P. 2011 LY2189265, a long-acting glucagon-like peptide-1 analogue, showed a dose-dependent effect on insulin secretion in healthy subjects

針對健康族群。

Shyangdan, D.S.

2010 Glucagon-like peptide analogues for type 2 diabetes mellitus: Systematic review and meta-analysis 內容不包含 dulaglutide 。

Chia, C.W. 2009 Role and development of GLP-1 receptor agonists in the management of diabetes 一般回顧評論性文章。

Ferdinand, K.C.

2014 Effects of the once-weekly glucagon-like peptide-1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus.

第二期臨床試驗。比較 dulaglutide 和 placebo 的血壓和心跳。

Spencer, K. 2012 Operational challenges and solutions with implementation of an adaptive seamless phase 2/3 study. 針對 adaptive 方法學的評論文章。

附錄三第三期隨機分派試驗的研究特徵

研究編號研究設計執行

metformin ≥ 1500 mg/day 穩定劑量≥ 3 個

研究編號研究設計執行

與 biguanide 和/或 sulfonylurea 併用 AWARD-2 多中心、隨機分派、

研究編號研究設計執行 mg、gliclazide 60-80 mg 或 glimepiride 2-3 mg）

和/或 biguanides

研究編號研究設計執行

與 metformin 和 pioglitazone（TZD）併用 AWARD-1 多中心、隨機分派、

與 insulin lispro 和/或 metformin 併用 AWARD-4 多中心、隨機分派、

研究編號研究設計執行

國家納入標準抗糖尿病治療排除標準導入期

主要療效指標測量點

治療期安全性追蹤期

臨界值為 0.40%。個中心量由分派前全日

insulin 劑量的 50%給起，其餘 50%給予 lispro 劑量。

排空異常、急性或慢性肝炎或有症狀的肝臟疾病、急性或慢性胰臟炎、GFR ≤ 30 mL/min/1.73m²、多發性內分泌腫瘤或有髓質 C 細胞增生、局部增生或癌病史或家族史、血清抑鈣素濃度 ≥ 20 pg/mL、器官移植。

註：HbA1c 指糖化血紅素（hemoglobin A1c）；OAM 為 oral antihyperglycemic medication（口服降血糖藥物）的縮寫。

附錄四試驗納入人數與完成治療人數

研究編號組別分派

人數

接受≥ 1 次劑量人數

主要療效評估點治療終點

完成人數未完成原因完成人數未完成原因

第 26 週第 52 週不良反應缺乏療效第 52 週第 78 週第 104 週不良反應缺乏療效死亡單方治療

AWARD-3

Dulaglutide 1.5 269 269 233 - 13 1 220 - - 14 2 -

Dulaglutide 0.75 270 270 242 - 6 2 218 - - 8 3 -

Metformin 268 268 226 - 10 4 213 - - 12 4 -

Miyagawa 2015

Dulaglutide 0.75 281 280 271 - 3 - - - -

Liraglutide 141 137 128 - 1 - - - -

Placebo 70 70 63 - 0 - - - -

與 metformin 併用

AWARD-5

Dulaglutide 1.5 304 304 258 - 21 2 238 - 192 63 4 1 Dulaglutide 0.75 302 302 268 - 12 0 243 - 184 64 0 0

Sitagliptin 315 315 270 - 14 2 238 - 186 65 4 2

Placebo/

Sitagliptin 177 177 124 - 24 6 112 - 95 39 6 1

AWARD-6 Dulaglutide 1.5 299 299 269 - 18 - - - -

Liraglutide 300 300 269 - 18 - - - -

與 biguanide 和/或 sulfonylurea 併用 AWARD-2

Dulaglutide 1.5g 273 273 - 248 8 - - 242 - 1 (52-78 週) - Dulaglutide 0.75 272 272 - 252 7 - - 243 - 1 (52-78 週) - Insulin glargine 265 262 - 240 4 - - 238 - 1 (52-78 週) -

研究編號組別分派人數

接受≥ 1 次劑量人數

主要療效評估點治療終點

完成人數未完成原因完成人數未完成原因

第 26 週第 52 週不良反應缺乏療效第 52 週第 78 週第 104 週不良反應缺乏療效死亡 Araki 2015 Dulaglutide 0.75 181 181 173 - 3 - - - -

Insulin glargine 180 180 171 - 1 - - - -

與 metformin 和 pioglitazone（TZD）併用

AWARD-1

Dulaglutide 1.5 279 279 260 - 8 1 245 - - 9 1 - Dulaglutide 0.75 280 280 263 - 4 0 254 - - 4 0 -

Exenatide 278 276 252 - 9 1 237 - - 10 2 -

Placebo 141 141 124 - 3 3 121 - -

1 (26-52 週期間，接受 dulaglutide 1.5 mg)

0 (26-52 週期間，

接受 dulaglutid e 1.5 mg)

與 insulin lispro 和/或 metformin 併用

AWARD-4

Dulaglutide 1.5 295 295 235 - - - 222 - - 31 1 0

Dulaglutide 0.75 293 293 243 - - - 224 - - 21 7 0

Insulin glargine 296 296 248 - - - 236 - - 9 2 3

附錄五各試驗的不良事件 Metformin ≥ 1500

mg/day 268 0 (0) - 39 Metformin ≥ 1500

mg/day 268 0 (0) 16

研究編號組別人

研究編號組別人與 biguanide 和/或 sulfonylurea 併用

AWARD-2

研究編號組別人

與 metformin 和 pioglitazone（TZD）併用

AWARD-1 與 insulin lispro 和/或 metformin 併用

AWARD-4

附錄六、經濟評估文獻搜尋紀錄

資料庫查詢日期關鍵字篇數

PubMed 2015.11.27 1 "dulaglutide"[Supplementary Concept] OR

"dulaglutide"[All Fields]

72 2 "economics"[Subheading] OR

"economics"[All Fields] OR "cost"[All Fields]

OR "costs and cost analysis"[MeSH Terms]

OR ("costs"[All Fields] AND "cost"[All Fields] AND "analysis"[All Fields]) OR "costs and cost analysis"[All Fields]

645,792

3 1#AND#2 4

Cochrane Library

2015.11.27 dulaglutide (Economic evaluations) 0 CRD 2015.11.27 1 Dulaglutide(CRD assessed economic

evaluation (bibliographic), CRD assessed economic evaluation (full abstract), HTA in progress, HTA published)

2 cost(CRD assessed economic evaluation (bibliographic), CRD assessed economic evaluation (full abstract), HTA in progress, HTA published)

19,214

3 1#AND#2 0

在文檔中易週糖注射劑 (頁 46-66)