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1型糖尿病患者胰岛素治疗中加用sotagliflozin的效果
Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes


Satish K. Garg ... 糖尿病 • 2017.12.14
相关阅读
• 1型糖尿病治疗指南更新

钠-葡萄糖协同转运蛋白抑制剂有望在1型糖尿病的治疗中发挥重要作用

 

翁建平

广东省糖尿病防治研究中心;中山大学糖尿病研究所;中山大学附属第三医院内分泌与代谢病学科


sotagliflozin是一种新型的钠-葡萄糖协同转运蛋白(SGLT)的抑制剂,它通过抑制SGLT-1从而延缓肠道葡萄糖的吸收,同时抑制SGLT-2减少肾脏葡萄糖吸收发挥效用。2017年9月在线发表(终稿发表于2017年12月14日的《新英格兰医学杂志》)的InTandem3研究1,是一项评估sotagliflozin在使用胰岛素治疗的1型糖尿病患者中的安全性和疗效的多中心、随机、双盲、安慰剂对照的临床3期研究。其结果提示联合胰岛素治疗的情况下,与安慰剂相比,sotagliflozin可使更多患者在达到良好血糖控制(HbA1c<7.0%)的同时,不发生严重低血糖和糖尿病酮症酸中毒,但sotagliflozin增加了糖尿病酮症酸中毒的风险。

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摘要


背景

大多数的1型糖尿病患者单纯使用胰岛素治疗难以获得合适的血糖控制。sotagliflozin是一种口服钠-葡萄糖协同转运蛋白-1和2的抑制剂。我们评价了在1型糖尿病患者中联用胰岛素和sotagliflozin的安全性和疗效。

 

方法

本研究是在全球133个中心开展的3期、双盲临床试验。我们纳入了1,402名正在接受任何形式胰岛素治疗(泵或注射)的1型糖尿病患者,并随机分配这些患者接受sotagliflozin(每日400 mg)或安慰剂治疗24周。主要终点是糖化血红蛋白在第24周时低于7.0%且在随机化后未发生严重低血糖或酮症酸中毒。次要终点包括与基线比较,糖化血红蛋白、体重、收缩压以及每日胰岛素单次推注剂量均值的变化值。

 

结果

sotagliflozin组患者达到主要终点的比例显著高于安慰剂组(699名患者中的200名[28.2%] vs. 703名中的107名[15.2%],P<0.001)。sotagliflozin组与基线比较下列指标变化值的最小二乘均数均显著大于安慰剂组,包括糖化血红蛋白(差值,-0.46个百分点)、体重(-2.98 kg)、收缩压(-3.5 mmHg)以及每日胰岛素单次推注剂量均值(每日-2.8个单位)(所有比较P均≤0.002)。sotagliflozin组与安慰剂组严重低血糖的发生率相似(分别为3.0%[21名患者] vs. 2.4% [17名])。与安慰剂组相比,有记录的血糖水平等于或低于55 mg/dL(3.1 mmol/L)的低血糖发生率在sotagliflozin组中显著较低。sotagliflozin组糖尿病酮症酸中毒的发生率高于安慰剂组(分别为3.0%[21名患者] vs. 0.6%[4名])。

 

结论

在使用胰岛素治疗的1型糖尿病患者中,接受sotagliflozin治疗者达到糖化血红蛋白小于7.0%,同时无严重低血糖或酮症酸中毒的比例高于接受安慰剂者。然而,sotagliflozin组有较高的糖尿病酮症酸中毒的发生率(本研究由Lexicon Pharmaceuticals资助,在ClinicalTrials.gov注册号为NCT02531035)。





作者信息

Satish K. Garg, M.D., Robert R. Henry, M.D., Phillip Banks, M.S., John B. Buse, M.D., Ph.D., Melanie J. Davies, M.D., Gregory R. Fulcher, M.D., Paolo Pozzilli, M.D., Diane Gesty-Palmer, M.D., Ph.D., Pablo Lapuerta, M.D., Rafael Simó, M.D., Ph.D., Thomas Danne, M.D., Darren K. McGuire, M.D., M.H.Sc., Jake A. Kushner, M.D., Anne Peters, M.D., and Paul Strumph, M.D.
From the University of Colorado Denver, Aurora (S.K.G.); the University of California at San Diego, San Diego (R.R.H.); Lexicon Pharmaceuticals, The Woodlands (P.B., D.G.-P., P.L., P.S.), the University of Texas Southwestern Medical Center, Dallas (D.K.M.), and Baylor College of Medicine and Texas Children’s Hospital, Houston (J.A.K.) — all in Texas; the Diabetes Research Center, University of North Carolina School of Medicine, Durham (J.B.B.); the University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, United Kingdom (M.J.D.); the University of Sydney, Sydney (G.R.F.); University Campus Bio-Medico of Rome, Rome (P.P.); Vall d’Hebron Research Institute, Barcelona, and CIBERDEM-Instituto de Salud Carlos III, Madrid (R.S.); Diabetes Center Auf der Bult, Hannover Medical School, Hannover, Germany (T.D.); and the University of Southern California, Los Angeles (A.P.). Address reprint requests to Dr. Satish Garg at the Barbara Davis Center for Diabetes, University of Colorado Denver, 1775 Aurora Court, Rm. M20-1323, Aurora, CO 80045, or at satish.garg@ucdenver.edu. A complete list of the inTandem3 primary investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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