钠-葡萄糖共转运体2抑制剂在治疗2型糖尿病中的应用

中国临床药理学与治疗学 ›› 2015, Vol. 20 ›› Issue (3): 338-343.

钠-葡萄糖共转运体2抑制剂在治疗2型糖尿病中的应用

胡秀卓, 吕莉

大连医科大学,辽宁 116044,大连

收稿日期:2014-05-21 修回日期:2014-07-23 出版日期:2015-03-26 发布日期:2015-04-08
通讯作者: 吕莉,女,副教授,研究方向:药理学。Tel: 0411-86110412 E-mail: lv_li@126.com
作者简介:胡秀卓,女,硕士在读,研究方向:临床医学。Tel: 0411-86110412 E-mail: 13478557016@163.com
基金资助:
辽宁省教育科学“十二五”规划课题(JG13DB325)

SGLT2 inhibitor for the treatment of type 2 diabetes mellitus

HU Xiu-zhuo, LV Li

Dalian Medical University, Liaoning 116044, Dalian,China

Received:2014-05-21 Revised:2014-07-23 Online:2015-03-26 Published:2015-04-08

摘要/Abstract

摘要： 糖尿病患者需要长期应用降糖药物控制血糖及防止并发症,因此研发疗效好、不良反应少的降糖药物尤为重要。钠-葡萄糖共转运体2(SGLT2)抑制剂为近些年来研究较多的一种用于2型糖尿病的新药物,有望在糖尿病患者的治疗中取得良好的效果。本文对该类药物的发展过程、代表药物、药理作用及不良反应等方面进行综述。

关键词: 糖尿病,2型, 钠-葡萄糖共转运体2抑制剂, canagliflozin, dapaglifozin

Abstract: Since the diabetic patients need to use anti-diabetic drugs to control serum glucose level and prevent complications for a long time, it's very important to discover a kind of drug which not only have good effect but also have less adverse drug reactions. In recent years,the SGLT2 inhibitor is well developed as a new kind of drug for type 2 diabetes, and is hopeful to acquire good therapeutic effect on diabetic patients. In this article we mainly describe the history, represent drugs, pharmacological effects and adverse reactions of this kind of drugs.

Key words: diabetes mellitus, type 2, SGLT2 inhibitor, canagliflozin, dapaglifozin

中图分类号:

R453.9

胡秀卓, 吕莉. 钠-葡萄糖共转运体2抑制剂在治疗2型糖尿病中的应用[J]. 中国临床药理学与治疗学, 2015, 20(3): 338-343.

HU Xiu-zhuo, LV Li. SGLT2 inhibitor for the treatment of type 2 diabetes mellitus[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(3): 338-343.

参考文献

[1] 陆菊明.糖尿病[M]//王吉耀,主编.内科学.2版.北京:人民卫生出版社,2010.8:1028-1029.
[2] Whiting DR, Guariguata L, Weil C, et al. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030 [J]. Diabetes Res Clin Pract, 2011,94(3):311-321.
[3] 刘永贵,田红,解学星,等. 治疗2型糖尿病的非胰岛素类药物的研究进展[J]. 现代药物与临床, 2013,34(2) 108-113.
[4] Lebastchi J, Deng S, Lebastchi AH, et al. Immune therapy and β-cell death in type 1 diabetes [J]. Diabetes, 2013,62(5):1676-1680.
[5] van Greevenbroek MM, Schalkwijk CG, Stehouwer CD. Obesity-associated low-grade inflammation in type 2 diabetes mellitus: causes and Consequences [J]. Neth J Med,2013,71(4):174-187.
[6] 何银辉,徐海燕,孙霞,等.2型糖尿病合理用药策略[J].中国临床药理学与治疗学,2011,16(7):837-840.
[7] Forxiga^TM(dapagliflozin), first-in-class SGLT2 that works independently of insulin, now approved in european union for treatment of type 2 diabetes[J]. Business Wire,2012.
[8] Elkinson S, Scott LJ. Canagliflozin: first global approval [J].Drugs,2013,73(9):979-988.
[9] Santer R, Calado J. Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target [J]. Clin J Am Soc Nephrol,2010,5(1):133-141.
[10]Ferrannini E, Solini A.SGLT2 inhibition in diabetes mellitus:rationale and clinical prospects[J]. Nat Rev Endocrinol,2012,8(8):495-502.
[11]Marsenic O. Glucose control by the kidney: an emerging target in diabetes [J]. Am J Kidney Dis,2009,53(5):875-883.
[12]Ehrenkranz JR, Lewis NG, Kahn CR, et al. Phlorizin: a review [J]. Diabetes Metab Res Rev,2005,21(1): 31-38.
[13]White JR,John R. Apple trees to sodium glucose co-transporter inhibitors: a review of SGLT2 inhibition [J]. Clinical Diabetes,2010,28(1):5-10.
[14]张文斌,龚念,王永祥. 肾脏SGLT2抑制剂:一类新型口服降血糖药物[J]. 生理科学进展,2010,41(6):453-456.
[15]Basile J.A new approach to glucose control in type 2 diabetes:the role of kidney sodium-glucose co-transporter 2 inhibition [J]. Postgrad Med,2011,123(4):38-45.
[16]Idris I,Donnelly R. Sodium-glucose co-transporter-2 inhibitors: an emerging new class of oral antidiabetic drug [J]. Diabetes Obes Metab,2009,11(2):79-88.
[17]Oku A,Ueta K,Arakawa K,et al.T-1095,an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes[J]. Diabetes,1999,48(9):1794-1800.
[18]Misra M. SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus [J]. J Pharm Pharmacol,2013,65(3):317-327.
[19]Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications [J]. Diabet Med,2010,27(2):136-142.
[20]Vallon V, Platt KA, Cunard R, et al.SGLT2 mediates glucose reabsorption in the early proximal tubule [J]. J Am Soc Nephrol,2011,22(1):104-112.
[21]DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia [J]. Diabetes Obes Metab,2012,14(1):5-14.
[22]Donnelly R. Canagliflozin: SGLT2 inhibitor for treating type 2 diabetes [J]. Future Prescriber,2013,14(1):5-7.
[23]Simonyi G. New possibility in the oral glucose lowering treatment of type 2 diabetesmellitus: sodium-glucose co-transporter-2 inhibitors [J]. Orv Hetil,2012,153(18):695-701.
[24]Berhan A, Barker A. Sodium glucose co-transport 2 inhibitors in the treatment of type 2 diabetes mellitus:a meta-analysis of randomized double-blind controlled trials[J]. BMC Endocr Disord, 2013, 13(1):58.
[25]List JF,Woo V,Morales E,et al. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes [J]. Diabetes Care,2009,32(4):650-657.
[26]Babu A. Canagliflozin for the treatment of type 2 diabetes [J]. Drugs Today (Barc) ,2013,49(6):363-376.
[27]Stenlof K, Cefalu WT,Kim KA,et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise[J]. Diabetes Obes Metab,2013,15(4):372-382.
[28]Johnsson KM, Ptaszynska A,Schmitz B,et al. Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin [J]. J Diabetes Complications,2013,27(5):479-484.
[29]Nicolle LE, Capuano G, Fung A,et al. Urinary tract infection in randomized phase III studies of canagliflozin, a sodium glucose co-transporter 2 inhibitor [J].Postgrad Med,2014,6(1):7-17.
[30]Nyirjesy P, Sobel JD, Fung A,et al.Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies [J].Curr Med Res Opin,2014 Feb 21,[Epub ahead of print].
[31]Nicolle LE,Capuano G,Ways K,et al.Effect of canagliflozin,a sodium glucose co-transporter 2 (SGLT2) inhibitor, on bacteriuria and urinary tract infection in subjects with type 2 diabetes enrolled in a 12-week,phase 2 study [J]. Curr Med Res Opin,2012,28(7): 1167-1171.
[32]Heise T,Seewaldt-Becker E,Macha S, et al. Safety,tolerability,pharmacokinetics and pharmacodynamics following 4 weeks' treatment with empagliflozin once daily in patients with type 2 diabetes [J]. Diabetes Obes Metab,2013,15(7):613-621.
[33]Vasilakou D, Karagiannis T,Athanasiadou E, et al. Sodium-glucose cotransporter 2 Inhibitors for type 2 diabetes:a systematic review and meta-analysis [J]. Ann Intern Med, 2013,159(4):262-274.
[34]Dietrich E,Powell J,Taylor JR. Canagliflozin: a novel treatment option for type 2 diabetes [J] .Drug Des Devel Ther,2013,7:1399-1408.
[35]Devineni D, Curtin CR, Polidori D,et al.Pharmacokinetics and Pharmacodynamics of Canagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, in Subjects With Type 2 Diabetes Mellitus[J]. J Clin Pharmacol,2013,53(6):601-610.
[36]Liang Y,Arakawa K,Ueta K,et al.Effect of canagliflozin on renal threshold for glucose,glycemia,and body weight in normal and diabetic animal models [J].PLoS One,2012,7(2):e30555.
[37]Polidori D, Sha S , Mudaliar S ,et al. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study [J]. Diabetes Care,2013,36(8):2154-2161.
[38]Rosenstock J, Aggarwal N, Polidori D,et al.Dose-ranging effects of canagliflozin,a sodium-glucose cotransporter 2 inhibitor,as add-on to metformin in subjects with type 2 diabetes [J].2012,35(6):1232-1238.
[39][No authors listed],Dapagliflozin (Forxiga) for type 2 diabetes[J]?Drug Ther Bull,2013,51(9):105-108.
[40]Yang L, Li H, Li H,et al. Pharmacokinetic and pharmacodynamic properties of single- and multiple-dose of dapagliflozin, a selective inhibitor of SGLT2, in healthy Chinese subjects [J].Clin Ther, 2013,35(8):1211-1222.e2.
[41]Han S,Hagan DL,Taylor JR,et al. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats [J].Diabetes,2008,57(6):1723-1729.
[42]Whaley JM,Tirmenstein M,Reilly TP,et al.Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus [J]. Diabetes Metab Syndr Obes,2012,5:135-148.
[43]Komoroski B,Vachharajani N,Boulton D,et al. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects [J]. Clin Pharmacol Ther, 2009,85(5):520-526.
[44]Ferrannini E, Ramos SJ, Salsali A,et al. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized,double-blind, placebo-controlled,phase 3 trial [J]. Diabetes Care, 2010,33(10):2217-2224.
[45]Bailey CJ,Gross JL,Hennicken D,et al.Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin:a randomized,double-blind,placebo-controlled 102-week trial [J]. BMC Med,2013,11(1):1-10.
[46]Plosker GL. Dapagliflozin:a review of its use in type 2 diabetes mellitus [J]. Drugs,2012,72(17):2289-2312.