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达格列净

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达格列净
Haworth projection (bottom)
臨床資料
读音/ˌdæpəɡlɪˈfloʊzɪn/ DAP-ə-glif-LOH-zin
商品名Forxiga, Farxiga, others
其他名稱BMS-512148; (1S)-1,5-anhydro-1-C4-chloro-3-[(4-ethoxyphenyl)methyl]phenylD-glucitol
AHFS/Drugs.comMonograph
核准狀況
懷孕分級
给药途径口服（錠劑）
藥物類別SGLT2抑制剂
ATC碼
法律規範狀態
法律規範
藥物動力學數據
生物利用度78%（投予10毫克劑量後）
血漿蛋白結合率~91%
药物代谢UGT1A9（主要）、CYP（次要）
代謝產物Dapagliflozin 3-O-glucuronide（非活性）
生物半衰期~12.9 小時
排泄途徑尿 (75%)、糞 (21%)[2]
识别信息
  • (2S,3R,4R,5S,6R)-2-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
CAS号461432-26-8  checkY
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.167.331 編輯維基數據鏈接
化学信息
化学式C21H25ClO6
摩尔质量408.873
3D模型（JSmol）
  • Clc1ccc(cc1Cc2ccc(OCC)cc2)[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O
  • InChI=1S/C21H25ClO6/c1-2-27-15-6-3-12(4-7-15)9-14-10-13(5-8-16(14)22)21-20(26)19(25)18(24)17(11-23)28-21/h3-8,10,17-21,23-26H,2,9,11H2,1H3/t17-,18-,19+,20-,21+/m1/s1 checkY
  • Key:JVHXJTBJCFBINQ-ADAARDCZSA-N checkY

达格列净（英語：Dapagliflozin，中文品牌名：安达唐(大陆地区)、福適佳(台灣地区)， 英文品牌名： Forxiga ）， 由阿斯利康研发，是第一种获批的SGLT2抑制剂，欧盟在2011年首先批准了此药物。2014年FDA批准其在美国销售。[3] 达格列净于2017年获得中国食品和药品监督管理总局批准，用于2型糖尿病成人患者改善其血糖控制。[4]

医疗用途

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达格列净可配合饮食和运动单药治疗，或和其他降糖药物连用。来改善二型糖尿病成人患者的血糖控制。研究表明，非糖尿病和二型糖尿病成年患者，当在现有治疗方案中加入达格列净或其他SGLT2抑制剂时，能够减缓肾小球滤过率下降和肾衰竭的进程。[5][6][7][8]

欧洲心脏病学会和美国心脏协会的治疗指南，认为SGLT2抑制剂可以作为射血分数降低（LVEF < 40%）[[心力衰竭]]患者的标准疗法。[9][10]这得到了两项大型随机对照试验[11][12]以及2023年的一项系统性回顾和荟萃分析的支持。[13]

多项研究证据表明，在标准心力衰竭治疗中加入达格列净及其他SGLT2抑制剂类药物，无论患者是否患有糖尿病，均可降低心力衰竭恶化、因心力衰竭住院以及心血管死亡的风险。[14][15][16][17][18][19]这些研究主要招募射血分数降低（LVEF < 40%）的患者。但是新的研究也表明，该药物对射血分数轻度降低或保留的患者也可能有一些益处。[20]SGLT2抑制剂能够降低因心血管疾病死亡，或心力衰竭住院和紧急就诊的风险。[21][22]一些荟萃分析和队列研究显示，在降低特定心力衰竭患者的住院风险上，达格列净可能比恩格列净等同类药物效果更好。然而，目前研究的结论尚不统一，仍需进一步的比较研究证实。[23][24][25]

达格列净不能用于治疗一型糖尿病，药品上市许可持有人撤回了本药在一型糖尿病的适应症。[26]和糖尿病酮症酸中毒，因为会增加中毒的风险。[27]

对于非糖尿病性慢性肾脏病

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2021年，FDA和EMA扩展了达格列净的适应症，批准其用于治疗患有慢性肾病但无糖尿病的患者。[28][29]

试验证实了该疗法具有以下效果：

DIAMOND 试验的结果显示，在六周的治疗期间中患者的蛋白尿没有改善。肾小球滤过率显著恶化，在停药后六周通常可逆。患者的体重降低了1.5公斤。[30][31]

DAPA-CKD 显示，在已经接受血管紧张素转换酶抑制剂（ACEI）或血管紧张素受体阻滞剂（ARBs）治疗的患者的中位治疗期 2.4 年中，治疗组比安慰剂组晚 8 个月左右出现肾脏滤过率持续下降、肾衰竭或死亡事件。然而，在治疗的前12至16个月期间，治疗组的肾脏滤过率低于安慰剂组，之后，其下降速度才开始略慢于安慰剂组。[32][31]

副作用

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由于达格列净导致严重的糖尿（有时每天约70克），因此可能导致体重迅速减轻和疲倦。 葡萄糖起渗透性利尿剂的作用（这种作用是糖尿病多尿的原因），可导致脱水。 尿液中葡萄糖含量的增加也可能使已经与糖尿病相关的感染恶化，特别是尿路感染及鹅口疮（念珠菌病）。 极少数情况下，使用SGLT2药物（包括达格列净）与会阴坏死性筋膜炎（也称为Fournier坏疽）有关。[33]

达格列净也与低血压反应有关。 人们担心它可能会增加糖尿病酮症酸中毒的风险。[34]

参考

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  3. ^ Liscinsky, Morgan. FDA approves Farxiga to treat type 2 diabetes. U.S. Food and Drug Administration. Jan 8, 2014 [15 April 2015]. （原始内容存档于2017-02-17）. 
  4. ^ 中国国家食品药品监督管理总局 2017年度药品审评报告. （原始内容存档于2019-11-06）. 
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  23. ^ McMurray, John J. V.; Solomon, Scott D.; Inzucchi, Silvio E.; Køber, Lars; Kosiborod, Mikhail N.; Martinez, Felipe A.; Ponikowski, Piotr; Sabatine, Marc S.; Anand, Inder S.; Bělohlávek, Jan; Böhm, Michael. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. The New England Journal of Medicine. 2019-11-21, 381 (21) [2025-10-28]. ISSN 1533-4406. PMID 31535829. doi:10.1056/NEJMoa1911303. 
  24. ^ Packer, Milton; Anker, Stefan D.; Butler, Javed; Filippatos, Gerasimos; Pocock, Stuart J.; Carson, Peter; Januzzi, James; Verma, Subodh; Tsutsui, Hiroyuki; Brueckmann, Martina; Jamal, Waheed. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. The New England Journal of Medicine. 2020-10-08, 383 (15) [2025-10-28]. ISSN 1533-4406. PMID 32865377. doi:10.1056/NEJMoa2022190. 
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  30. ^ Cherney, David Z. I.; Dekkers, Claire C. J.; Barbour, Sean J.; Cattran, Daniel; Abdul Gafor, Abdul Halim; Greasley, Peter J.; Laverman, Gozewijn D.; Lim, Soo Kun; Di Tanna, Gian Luca; Reich, Heather N.; Vervloet, Marc G. Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial. The Lancet. Diabetes & Endocrinology. 2020-07, 8 (7) [2025-10-28]. ISSN 2213-8595. PMID 32559474. doi:10.1016/S2213-8587(20)30162-5. 
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  32. ^ Heerspink, Hiddo J. L.; Stefánsson, Bergur V.; Correa-Rotter, Ricardo; Chertow, Glenn M.; Greene, Tom; Hou, Fan-Fan; Mann, Johannes F. E.; McMurray, John J. V.; Lindberg, Magnus; Rossing, Peter; Sjöström, C. David. Dapagliflozin in Patients with Chronic Kidney Disease. The New England Journal of Medicine. 2020-10-08, 383 (15) [2025-10-28]. ISSN 1533-4406. PMID 32970396. doi:10.1056/NEJMoa2024816. 
  33. ^ Research, Center for Drug Evaluation and. FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes. FDA. 9 February 2019 [2019-11-06]. （原始内容存档于2021-03-08） –通过www.fda.gov. 
  34. ^ Safety Alerts for Human Medical Products — SGLT2 inhibitors: Drug Safety Communication — FDA Warns Medicines May Result in a Serious Condition of Too Much Acid in the Blood. Food and Drug Administration. 15 May 2015 [15 November 2016]. （原始内容存档于2017-04-06） （英语）. 
检索自“https://zh.wikipedia.org/w/index.php?title=达格列净&oldid=89718418”